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Biomedical subjects

Y F Chen

Publications and source records attributed to Y F Chen.

At least 91 records · Page 5Linked to original sources

Drug utilization pattern of antiepileptic drugs and traditional Chinese medicines in a general hospital in Taiwan - a pharmaco-epidemiologic study.

OBJECTIVE: Studies on antiepileptic drug utilization are important for the optimization of drug therapy and drug control. The present study was to evaluate the drug utilization pattern of standard antiepileptic drugs and traditional Chinese medicines (TCMs) in the treatment of different types of epilepsy in a general hospital in Taiwan. METHOD: The epileptic patients under antiepileptic drug treatment at Veterans General Hospital-Taipei were considered in the analysis. Current diagnosis was obtained by the neurologist in charge of the patient. All patients were interviewed by standard questionnaire designed to provide specific information on the types of antiepileptic drugs and details of their use. The questionnaire also sought to determine whether TCMs were used, and whether patients were using TCMs in combination with hospital standard treatment. The results were analysed by descriptive statistics. RESULTS: 729 patients with epilepsy definitely diagnosed were analysed in the study. 445 patients (61.04%) were prescribed with one antiepileptic drug. Combinations of two antiepileptic drugs were prescribed to 261 patients (35.80%), and combinations of three or more antiepileptic drugs to 23 patients (3.16%). A total of 1039 antiepileptic drugs was prescribed, corresponding to an average 1.42 drugs per patient. The most frequently prescribed antiepileptic drug was carbamazepine (56.93%), followed by phenytoin (31.96%), valproate (30.73%) and clonazepam (14.13%). Among the 729 epileptic patients, 83.68% used standard antiepileptic drugs alone, 16.32% used antiepileptic drugs in combination with TCMs. CONCLUSION: Monotherapy is the type of therapy most frequently used in all types of seizures. The selection of antiepileptic drugs is based on efficacy for specific seizure types and epileptic syndromes. The most frequently prescribed antiepileptic drug was carbamazepine, followed by phenytoin, valproate and clonazepam. As some of the patients used TCMs for treatment of epilepsy even when scientific medicine has been provided, further studies on the possible interactions between TCMs and antiepileptic drugs are in progress.

Adult↗

Efficacy of latanoprost as an adjunct to medical therapy for residual angle-closure glaucoma after iridectomy.

Residual primary angle-closure glaucoma (PACG) after iridectomy is an important issue among Asians, especially Chinese. In this study, we tested the effectiveness of latanoprost as an intraocular pressure (IOP) lowering agent in cases of residual PACG. Twenty-six eyes of 26 PACG patients with persistently elevated IOP after iridectomy, despite treatment with conventional IOP lowering drugs (beta blockers and pilocarpine) were included. Latanoprost 0.005%, one drop daily, was added adjunctively to all eyes. Measurement of IOP at baseline and after the start of treatment with latanoprost indicated a significant IOP reduction. The IOP decreased by about 21% (p < 0.005) during the first 3 months, and showed a reduction of about 36% at the end of 1 year. At the 1-year follow up, the IOP was well controlled (below 20 mmHg) in all eyes. These findings show that, in combination with beta blockade and pilocarpine, latanoprost can ameliorate residual PACG after iridectomy and could potentially forestall the need for further therapeutic intervention.

Adjuvants, Pharmaceutic↗

Endothelial dysfunction in the pulmonary vascular bed.

The pulmonary endothelium modulates vascular tone by the release of endothelium-derived constricting (EDCF) and relaxing (EDRF) factors, among them endothelin-1, nitric oxide, prostacyclin, and putative endothelium-derived hyperpolarizing factors. Abnormalities in EDCF and EDRF generation have been demonstrated in a number of cardiopulmonary disease states, such as primary and secondary pulmonary hypertension, chronic obstructive lung disease, cardiopulmonary bypass, and congestive heart failure. An imbalance between EDCF and EDRF, termed "pulmonary endothelial dysfunction," may contribute to the alteration in vascular tone characteristic of pulmonary disease. The following review summarizes the present knowledge of the role of EDCF and EDRF in such processes with major focus on pulmonary endothelial dysfunction in hypoxia-induced pulmonary hypertension.

Animals↗

Evaluation of low-dose endotoxin administration during pregnancy as a model of preeclampsia.

BACKGROUND: Recent evidence implicates nitric oxide (*NO) in the pathogenesis of preeclampsia. The authors tested the hypothesis that administration of low-dose endotoxin to pregnant rats mimics the signs of preeclampsia in humans and that *NO and *NO-derived species play a role in that animal model. METHODS: Endotoxin was infused at doses of 1, 2 and 10 microg/kg over 1 h to rats on day 14 of pregnancy. Mean arterial pressure, urinary protein, urinary and plasma nitrite plus nitrate (NO2- + NO3-) concentrations, and platelet count were measured before and after the endotoxin infusion. In another group of pregnant rats, the nitric oxide synthase inhibitor L-nitroarginine methyl ester (L-NAME) was administered in drinking water at a dose of 3 mg x kg(-1) x d(-1) starting on day 7 of pregnancy. Endotoxin was then infused at 10 microg/kg on day 14 of pregnancy. Kidneys and uteroplacental units were examined histologically and analyzed immunohistochemically for 3-nitrotyrosine. RESULTS: Endotoxin administration at doses of 2 and 10 microg/kg caused proteinuria and thrombocytopenia in pregnant rats, but did not result in hypertension. Urinary NO2- + NO3- concentration, reflective of tissue *NO production rates, was significantly elevated in pregnant rats that received endotoxin at 10 microg/kg. Ingestion of L-NAME caused hypertension. Tissues from pregnant rats treated with L-NAME, endotoxin at 10 microg/kg, and a combination of L-NAME and endotoxin had increased 3-nitrotyrosine immunoreactivity. CONCLUSION: Nitric oxide either directly or through secondary species plays a significant role in the biochemical and physiologic changes that occur in a rodent model of endotoxin-induced injury.

Animals↗

Endothelin and pulmonary hypertension.

Biochemical and molecular biological evidence indicates that endothelin (ET)-1 and its receptors are selectively upregulated in the lung during exposure to hypoxia, while functional evidence indicates that ET-1 is a major mediator of hypoxia-induced pulmonary vasoconstriction and vascular remodeling. Hypoxia stimulates ET-1 gene transcription and peptide synthesis in cultured endothelial cells, and plasma ET-1 levels are increased in patients with primary pulmonary hypertension, and in humans exposed to high altitude, while immunoreactive ET-1 and ET-1 mRNA levels are increased in pulmonary artery endothelial cells of patients with primary pulmonary hypertension. Rats exposed to normobaric hypoxia exhibit increased pulmonary artery pressure, increased ET-1 peptide levels in plasma and lung, and selective increases in steady-state ET-1 and ET(A) and ET(B) receptor mRNA levels in lung but not in organs perfused by the systemic vasculature. The observations that both ET-1 and its major vascular smooth-muscle cell receptor are upregulated in response to hypoxia suggest that ET-1 may be a mediator of hypoxia-induced pulmonary hypertension. Moreover, hypoxic pulmonary vasoconstriction and vascular remodeling can be prevented and reversed by administration of either an ET(A)-selective or a combined ET(A) and ET(B) receptor antagonist. These findings support the hypothesis that endogenous ET-1 plays a major role in hypoxic pulmonary vasoconstriction/hypertension, right heart hypertrophy, and pulmonary vascular remodeling and suggest that ET-receptor blockers may be useful in the treatment and prevention of hypoxic pulmonary hypertension in humans.

Animals↗

Transplant of cultured autologous pure melanocytes after laser-abrasion for the treatment of segmental vitiligo.

Segmental vitiligo is a special type of vitiligo with unilateral distribution of lesions and has a stable course. Clinically, many patients with segmental vitiligo have unsatisfactory responses to topical corticosteroid or UV phototherapy. We have developed a technique for the isolation of melanocytes from a small specimen of normally pigmented skin obtained via a suction blister. The melanocytes can be proliferated in culture and then replanted onto laser-abrased vitiliginous areas. We used this procedure to treat 25 patients with segmental vitiligo that were refractory to medical therapy. The repigmented portion of the total treated area amounted to 95-100% in 21 patients and 65 to 94% in 4 patients. The response rate to treatment was 100% in this study. No scarring or other side-effects developed. The results of this study demonstrate that this method is a valuable tool for the treatment of patients with segmental vitiligo.

Adolescent↗

Hypoxia reduces atrial natriuretic peptide clearance receptor gene expression in ANP knockout mice.

We tested the hypotheses that hypoxic exposure is associated with exacerbated pulmonary hypertension and right ventricular (RV) enlargement, reduced atrial natriuretic peptide (ANP) clearance receptor (NPR-C) expression, and enhanced B-type natriuretic peptide (BNP) expression in the absence of ANP. Male wild-type [ANP(+/+)], heterozygous [ANP(+/-)], and homozygous [ANP(-/-)] mice were studied after a 5-wk hypoxic exposure (10% O(2)). Hypoxia increased RV ANP mRNA and plasma ANP levels only in ANP(+/+) and ANP(+/-) mice. Hypoxia-induced increases in RV pressure were significantly greater in ANP(-/-) than in ANP(+/+) or ANP(+/-) mice (104 +/- 17 vs. 45 +/- 10 and 63 +/- 7%, respectively) as were increases in RV mass (38 +/- 4 vs. 26 +/- 5 and 29 +/- 4%, respectively). NPR-C mRNA levels were greatly reduced in the kidney, lung, and brain by hypoxia in all three genotypes. RV BNP mRNA and lung and kidney cGMP levels were increased in hypoxic mice. These findings indicate that disrupted ANP expression worsens hypoxic pulmonary hypertension and RV enlargement but does not alter hypoxia-induced decreases in NPR-C and suggest that compensatory increases in BNP expression occur in the absence of ANP.

Animals↗

Simultaneous determination of unbound cefoperazone in rat blood and brain using microdialysis.

A sensitive microbore HPLC method was developed for the simultaneous determination of unbound cefoperazone in rat blood and brain using microdialysis. Two microdialysis probes were inserted into the jugular vein/right atrium and brain striatum of Sprague-Dawley rats. Cefoperazone (50 mgkg(-1), i.v.) was then administered via the femoral vein. Blood and brain dialysates were collected and eluted with a mobile phase containing methanol-100 mM monosodium phosphoric acid (30:70, v/v, pH 5.5). The wavelength of the UV detector was set at 254 nm. The detection limit of cefoperazone was 20 ng mL(-1). Isocratic separation of cefoperazone was achieved within 10 min. The intra- and inter-assay accuracy and precision of the analyses were < or =10% in the range of 0.05-10 microg mL(-1). The ratio of the area under the concentration curve of cefoperazone in rat brain and blood was estimated to be about 7-8%. It is concluded that cefoperazone is capable of penetrating the blood-brain barrier.

Animals↗

Partial anomalous pulmonary venous connection draining into superior vena cava--two cases reports.

Anomalous pulmonary venous connection is a relatively common associated anomaly in patients with atrial septal defect (ASD), particularly among those with the sinus venosus type. The incidence of partial anomalous pulmonary venous connection (PAPVC) is higher than 0.7% in the general population and 10% in patients with ASD. In this study, we present two cases with initial impression of ASD, the sinus venosus type in one and the secundum type in the other. The one with the sinus venosus type was found to have a PAPVC that drained into SVC, and the other was suspected of having the same problem because an abnormal shunt was found during cardiac catheterization. This speculation could not be proved, however, due to transesophageal echocardiogram failure. Because we feared the possibility of cardiac defects other than ASD, we performed a minimally invasive operation using a small midline incision instead of the submammary incision and did a full median sternotomy on the patient to look for other complicating coexistent cardiac defects. This patient and the former one were both proven intraoperatively to have a PAPVC that drained into SVC with sinus venosus ASD. The operation to correct an ASD is a rudimentary procedure, and it often becomes a common type of minimally invasive operation among young cardiac surgeons with limited experience. A submammary incision under the impression of simple ASD may meet with certain complications. Therefore, after our experience with the latter case, we do the minimally invasive operation using a small midline incision, which can be easily extended if need be.

Adult↗

Discrete subaortic membranous stenosis--a case report.

Isolated subaortic stenosis is a rare type of cardiac anomaly which has been characterized as having two types: the discrete type, including membranous or fibromuscular, and the tunnel type. In the discrete type, a crescent-shaped, fibrous curtain is attached to the ventricular septum or completely encircles the left ventricular outflow tract and can be located anywhere from immediately below the aortic valve to 10 mm or more into the body of ventricle. A 22-year-old female presented at our hospital with a divided PDA, a murmur that was found by incident and progressive exertional dyspnea. Echocardiography revealed left ventricular hypertrophy, moderate aortic insufficiency, and severe aortic stenosis characterized by a thickened aortic valve and membranous type subaortic stenosis with a transmembranous high pressure gradient, 121 mmHg. An operation to replace the aortic valve and excise the membranous collar was performed with cardiopulmonary bypass support. The patient did well during the postoperative follow-up period. If the preoperative LVOT pressure gradient had been higher than 45 mmHg, the incidence of recurrent stenosis, progression of aortic regurgitation and the need for reoperation would have been higher. In order to prevent this from happening, we chose to replace the defective valve with a mechanical valve and enucleate the discrete lesion.

Adult↗

Simultaneous measurement of cefuroxime in rat blood and brain by microdialysis and microbore liquid chromatography. Application to pharmacokinetics.

To characterize the pharmacokinetics of cefuroxime in rat blood and brain, microdialysis probes were inserted into the jugular vein and brain striatum, respectively. Cefuroxime (20 mg/kg, i.v.) was administered via the femoral vein. Blood microdialysates were automatic injected onto microbore liquid chromatography via an on-line injectors. The mobile phase consisted of methanol-100 mM monosodium phosphoric acid (25:75, v/v, pH 5.0) with a flow-rate of 0.05 ml/min. Ultraviolet detector was set at a wavelength of 280 nm for cefuroxime. The present assay enhanced the detection sensitivity and enabled the determination of cefuroxime down to 5 ng/ml. The pharmacokinetic data demonstrated that the area under the concentration curve (AUC) ratio of unbound cefuroxime in rat brain and blood was about 4.2% after cefuroxime (20 mg/kg, i.v.) administration. These results provided further evidence that cefuroxime could penetrate the blood-brain barrier.

Animals↗

Estrogen inhibits vascular smooth muscle cell-dependent adventitial fibroblast migration in vitro.

BACKGROUND: Mounting experimental evidence suggests that estrogen treatment protects against neointima formation in response to vascular injury in vivo. Previous studies have suggested that this process includes the activation and migration of adventitial fibroblasts. The present in vitro study was designed to establish a mechanism whereby estrogen attenuates migration of adventitial fibroblasts. METHDS AND RESULTS: Primary cultures of vascular smooth muscle cells (VSMCs) and adventitial fibroblasts were derived from female Sprague-Dawley rats. Reverse transcriptase-polymerase chain reaction and Western blotting were used to determine that expression of the estrogen receptor (ER) was restricted to early-passage VSMCs. Migration of transduced (retrovirally mediated) fibroblasts was determined by counting the number of blue lacZ-expressing cells attached to Boyden-type chambers preconditioned under defined experimental conditions. Compared with growth medium alone, chambers treated with medium conditioned by VSMCs demonstrated a 2-fold increase in fibroblast migration, suggesting that VSMCs release soluble factor(s) competent to bind the Transwell membrane and promote fibroblast migration. In contrast, treatment of VSMCs with 17beta-estradiol (10(-9) to 10(-7) mol/L) before preconditioning of the chamber induced a dose-dependent inhibition of fibroblast migration. Cotreatment of VSMCs with 17beta-estradiol and the ER antagonist ICI-182780 (10(-7) mol/L) blocked the inhibitory effect of estrogen on fibroblast migration. CONCLUSIONS: These observations suggest a novel mechanism of hormonal vasoprotection by which estrogen directly modulates VSMC expression of factor(s) controlling migration of adventitial fibroblasts via an ER-dependent mechanism.

Animals↗

Determination of unbound 20(S)-camptothecin in rat bile by on-line microdialysis coupled to microbore liquid chromatography with fluorescence detection.

To evaluate the biliary excretion of unbound camptothecin, a flow-through microdialysis probe was constructed for bile sampling. The shunt linear probe was connected from the bile duct, between the liver side to the duodenum to avoid obstruction of the bile duct or bile salt waste. For automatic analysis of microdialysate, an on-line injector was connected to a microbore high-performance liquid chromatographic column with fluorescence detection. Samples were eluted with a mobile phase containing methanol-100 mM monosodium phosphoric acid (35:65, v/v, pH 2.5, adjusted with orthophosphoric acid). The limit of quantification was 1 ng/ml for camptothecin. Following camptothecin administration (5 mg/kg, i.v.), it was found in the bile microdialysate. It was concluded that the in vivo microdialysis technique yields useful data on the biliary excretion of camptothecin. This method is suitable for additional pharmacokinetic studies in rat bile.

Animals↗

Measurement of unbound caffeic acid in rat blood by on-line microdialysis coupled with liquid chromatography and its application to pharmacokinetic study.

To monitor the levels of caffeic acid in rat blood, an on-line microdialysis system coupled with liquid chromatography was developed. The microdialysis probe was inserted into the jugular vein/right atrium of male Sprague-Dawley rats. Caffeic acid (100 mg/kg, i.v.) was then administered via the femoral vein. Dialysates were automatically injected onto a liquid chromatographic system via an on-line injector. Samples were eluted with a mobile phase containing methanol-100 mM monosodium phosphoric acid (35:65, v/v, pH 2.5). The UV detector wavelength was set at 320 nm. The detection limit of caffeic acid was 20 ng/ml. The in vivo recoveries of the microdialysis probe for caffeic acid at 0.5 and 1 microg/ml were 48.34+/-2.68 and 47.64+/-3.43%, respectively (n=6). Intra- and inter-assay accuracy and precision of the analyses were < or = 10% in the range of 0.05 to 10 microg/ml. Pharmacokinetics analysis of results obtained using such a microdialysis-chromatographic method indicated that unbound caffeic acid in the rat fitted best to a biexponential decay model.

Animals↗

Involvement of lipids in ferriprotoporphyrin IX polymerization in malaria.

Approximately 70% of the initial ferriprotoporphyrin IX polymerizing activity in cell-free preparations of erythrocytes infected with Plasmodium berghei was recovered in a chloroform extract. No polymerizing activity remained in the residue. In studies to identify substances that promote FP polymerization, arachidonic, linoleic, oleic, and palmitoleic acids, 1-mono- and di-oleoylglycerol, and the detergents, SDS, Tween 80, and n-octyl-glucopyranoside, were active. Tri-oleoylglycerol, cholesterol, di-oleoylphosphatidylethanolamine, and stearic and palmitic acids were inactive. The model lipid, mono-oleoylglycerol (250 nmol), co-precipitated with FP from a 0.09 M acetate medium at pH 5 and promoted the polymerization of 215 nmol (61%) of the ferriprotoporphyrin IX in the precipitate during a 24-h incubation at 37 degrees C. Polymerization was maximal at pH 5, it was approximately linear for 2 h, and it continued at a decreasing rate for 24 h. The polymer contained exclusively ferriprotoporphyrin IX (97+/-1.3%, mean+/-S.E., n=4) and exhibited the solubility and the electronic absorption and infrared spectral characteristics of the sequestered ferriprotoporphyrin IX of hemozoin. Detergents presumably promote polymerization in an acid medium by helping to dissolve monomeric FP. We suggest that unsaturated lipids co-precipitate with FP in the parasite's acidic food vacuole and also dissolve sufficient monomeric FP to allow polymerization.

Animals↗

An aqueous concentration model for riverine spills.

A numerical model is developed to predict the aqueous concentrations of sparingly soluble compounds resulting from oil, fuel, or chemical spills onto rivers. The model computes the concentration of compounds both in the slick phase and in the aqueous phase by simulating the processes that affect the fate of the spilled compound. Processes simulated by the model include spreading and drifting of the surface slick, evaporation from the slick, dissolution from the slick into the water, volatilization from the water, and longitudinal dispersion in the river. The model is used to simulate a hypothetical spill of jet fuel, demonstrating that the concentration of a compound in the aqueous phase is strongly linked to its concentration in the slick phase. The most soluble and most volatile compounds exhibit the highest aqueous concentrations in the early stages of the spill, but ultimately the less soluble and less volatile compounds reach the highest aqueous concentrations. Streamwise concentration gradients in the slick due to the rapid evaporation of the more volatile compounds are shown to have an effect on the aqueous concentration.

Aircraft↗

Differential expression of natriuretic peptides and their receptors in volume overload cardiac hypertrophy in the rat.

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) upregulation are genetic markers for the chronic hypertrophic phenotype but also have important acute physiologic effects on salt and water balance and blood pressure control. The presence of a dual NP-system led us to hypothesize a differential expression of ANP and BNP in response to an acute hemodynamic stress of volume overload in the left ventricle (LV) and right ventricle (RV). Accordingly, we examined the temporal relationship between the RV and LV expression of ANP and BNP mRNA and NP receptor mRNA levels on days 1, 2, 3, and 7 after induction of aortocaval fistula in the rat. LV end-diastolic pressure was increased 1.5-fold by day 3 and 2.0-fold by day 7 compared to control (P<0.05). LV weight increased by day 7 compared to control (2.34+/-0.04 vs 3.07+/-0.10 mg/g, P<0.05) while RV weight did not change over the 7 days. There was a 7-fold increase of ANP mRNA in LV at day 1, which was sustained through day 7, while LV BNP mRNA levels did not differ from controls over the 7 days. In contrast, RV mRNA transcript levels for ANP and BNP were increased >2-fold by day 2 and this increase was sustained throughout 7 days. NP clearance receptor was decreased by 75% by day 7 in the LV but did not change in the RV. Thus, LV ANP mRNA levels increased before the onset of LV hypertrophy and RV BNP mRNA levels increased in the absence of RV hypertrophy. The disparate response of BNP and the NP clearance receptor transcript levels in the LV and RV may be related to differences in load and/or differential expression of the NP system in the LV and RV in response to acute haemodynamic stress.

Animals↗

Estrogen attenuates the adventitial contribution to neointima formation in injured rat carotid arteries.

OBJECTIVE: This study tested, in ovariectomized rats, whether (1) adventitial activation plays a role in the vascular injury response, and (2) inhibition of adventitial activation and the subsequent wave of cell proliferation moving from adventitia to neointima contributes to the estrogen-induced attenuation of neointima formation in balloon injured carotid arteries. METHODS: Ovariectomized Sprague-Dawley rats were treated with either 17 beta-estradiol or vehicle beginning 72 h prior to balloon injury of the right common carotid artery and were sacrificed at 0, 3, 7, 14 and 28 days after injury. BrdU was administered 18 h and 12 h prior to sacrifice in order to quantitate mitotic activity in adventitia, media and neointima of the damaged vessel at specified times post injury. RESULTS: Adventitial activation, evidenced by positive BrdU staining, was evident on the day of injury, peaked on day 3 and was resolved by day 7, thus preceding neointima formation. Numbers of BrdU labeled cells in adventitia on day 3 were significantly reduced in estrogen treated rats compared to controls. BrdU labeled cells were undetectable in media on the day of injury, appeared at day 3 and disappeared by day 14. Neointima appeared at day 7 and increased in area throughout the period of observation. Neointimal area and numbers of BrdU labeled cells in neointima were significantly reduced in estrogen treated rats compared to controls. These findings suggest that there is a wave of cell proliferation moving in an adventitia-to-lumen direction following endoluminal injury of the rat carotid artery and that estrogen modulates this proliferative response to injury. CONCLUSION: These results support the hypothesis that adventitial activation contributes to the vascular injury response and that estrogen reduces this contribution.

Analysis of Variance↗