bluuebunny/crossref_metadata_2025_split huggingface dataset:
The in vitro Inhibitory Effect of Tannin Derivatives on 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase on Vero Cells
Authors: Chang Jun-Jen , Chen Tso-Hsiao , Chan Paul , Chen Yi-Jen , Hsu Feng-Lin , Lo Ming-Yu , Lin Jung-Yaw 
Published: April 2003

Coronary heart disease is still the major cause of death in industrialized countries. Multiple primary or secondary interventional trials to lower serum cholesterol in humans have resulted in significant reduction of coronary events and death, one of the major reasons attributed to developing a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor such as pravastatin. Developing new inhibitors of cholesterol synthesis is still common in the pharmaceutical industry. Tannin comprises a large group of natural polyphenolic compounds possessing antioxidant effects. The methods for analysis of specific inhibitors of mevalonate biosynthesis have already been well established by using Vero cells, a cell line obtained from kidneys of African green monkeys. Tannin derivatives isolated from different traditional Chinese herbs were dissolved in DMSO and incubated with Vero cells with or without the addition of 1 mmol/l mevalonate or 5 mmol/l sodium acetate for 24 h in order to observe cell growth. Pravastatin, a specific HMG-CoA reductase inhibitor, was used as positive control which could inhibit Vero cells growth effectively and cell growth inhibition was reversible after adding 1 mmol/l mevalonate. More than 50 tannin derivatives were used for the study, but only two compounds – proanthrocyanidin A-2 (belonging to the flavan-3-ol group) and 1,2,3,6-tetra-O-galloyl-β-<i>D</i>-glucose (belonging to the gallotannin group) – showed significant growth inhibition of Vero cells. This study showed that some isolated tannin derivatives from traditional herbs were effective HMG-CoA reductase inhibitors which might be developed into new hypocholesterolemic agents.
Effects of Taurine on Cerulein-Induced Acute Pancreatitis in the Rat
Authors: Ahn Byung Ok , Kim Kwang Hee , Lee Goo , Lee Hong Sik , Kim Chang Duck , Kim Young Sik , Son Mi Won , Kim Won Bae , Oh Tae Young , Hyun Jin Hai 
Published: April 2003

Taurine, or 2-aminoethane sulfonic acid, is an intracellular amino acid and has been suggested to have a function in protecting biological systems from oxidative tissue damage. The aim of this study was to determine the effect of taurine against cerulein-induced acute pancreatitis in rats. Acute pancreatitis was induced by administering three subcutaneous injections of cerulein (40 µg/kg body weight) at 1-hour intervals, while taurine was administered intravenously at graded doses (30, 100, or 300 mg/kg, respectively) following the first cerulein injection. The severities of pancreatitis and lung injury were determined by measuring biochemical parameters, tissue myeloperoxidase (MPO), and histological changes. To clarify the mechanism of taurine, serum IL-1β and TNF-α levels and tissue concentrations of malondialdehyde (MDA) were evaluated. In cerulein-induced acute edematous pancreatitis, treatment with taurine significantly decreased hyperamylasemia, tissue MPO, pancreatic edema, and the extent of pancreatic and pulmonary injury. Taurine decreased MDA concentration in the pancreas and lung, but not the serum cytokine concentration. We would conclude that taurine has beneficial effects in cerulein-induced acute pancreatitis and lung injuries by preventing the production of oxygen free radicals.
Angiotensin-Induced Enhancement of Excitatory Junction Potentials Evoked by Periarteriolar Nerve Stimulation and Vasoconstriction in Rat Mesenteric Arteries Are Both Mediated by the Angiotensin AT1 Receptor
Authors: Ziogas James , Vessey Kirstan 
Published: April 2003

The aims of the present study were to determine the angiotensin II (AngII) receptor subtype(s) involved in vasoconstriction and enhancement of sympathetic neurotransmission in rat isolated mesenteric arteries. Vasoconstriction was assessed in mesenteric artery ring preparations suspended under 0.5 g of tension in a myograph. In control arteries, with an intact endothelium, AngII (1 nmol/l–3 µmol/l) caused a concentration-dependent contraction. The pEC<sub>50</sub> for AngII was 7.6 ± 0.2 and the maximum response of 0.24 ± 0.07 g was reached with 100 nmol/l. In the presence of indomethacin (3.0 µmol/l) and N<sup>ω</sup>-nitro-<i>L</i>-arginine (NOLA) (100 µmol/l) to remove the influence of endothelium-derived prostaglandins and nitric oxide, the maximum response evoked by AngII was increased to 0.48 ± 0.1 g and the pEC<sub>50</sub> was 7.6 ± 0.3. The AT1 receptor antagonist losartan (30 nmol/l) competitively blocked the AngII-induced contractions with an estimated pA<sub>2</sub> of 8.2 in both the control arteries and in arteries treated with indomethacin and NOLA. The AT2 receptor antagonist PD 123319 (1 µmol/l) did not affect AngII-induced contractions under either condition. Conventional intracellular microelectrode recording techniques were used to investigate the effects of AngII on excitatory junction potentials (EJP) evoked by stimulation of periarteriolar sympathetic nerves. Stimulation with trains of 10 pulses delivered at 0.9 Hz evoked EJP which were blocked by tetrodotoxin (0.1 µmol/l), guanethidine (30 µmol/l) and the P<sub>2X</sub> receptor desensitizing agent α,β-methylene ATP (30 µmol/l) suggesting the EJP were mediated by ATP, or a related purine, released from sympathetic nerves. AngII (0.3– 100 nmol/l) did not affect the resting membrane potential or the amplitude of the first EJP, but did enhance the amplitude of the plateau EJP later in the train. A maximum 49.2 ± 3.9% enhancement of the plateau EJP amplitude was elicited by 10 nmol/l AngII and the pEC<sub>50</sub> was 9.1 ± 0.1. The facilitatory effect of AngII on EJP amplitude was not altered in the presence of indomethacin and NOLA. Losartan (30 nmol/l) competitively blocked the AngII-induced enhancement of plateau EJP amplitude, with an estimated pA<sub>2</sub> of 8.6. PD 123319 did not alter the enhancement of plateau EJP amplitude by AngII. The results from the present study show that both the vasoconstriction and enhancement of plateau EJP amplitude by AngII in rat mesenteric arteries are blocked by the AT1 receptor antagonist losartan and are unaffected by the AT2 receptor antagonist PD 123319.
Effects of Adenosine on Thrombosis and Thrombolysis in a Canine Experimental Preparation
Authors: Huang Jinbao , Feldbaum Victor M. , Lucchesi Benedict R. , Werns Steven W. 
Published: April 2003

Intracoronary infusion of adenosine is reported to inhibit cyclic flow variations after coronary artery injury and stenosis. This study was performed in the anesthetized dog to determine if adenosine prevents arterial thrombosis and/or reocclusion after thrombolysis. Carotid and coronary arteries were instrumented with Doppler<sup>TM</sup> flow probes, a critical stenosis, infusion line and an anodal electrode. Two protocols were employed. In the thrombosis protocol, intracarotid infusion of adenosine (20 µg/kg/min for 3 h) did not alter cyclic flow variations or patency during induction of vessel wall injury. In the second protocol, occlusive arterial thrombi were induced by anodal current injury and lysed with local application of tissue plasminogen activator. Whereas adenosine prolonged the time to arterial occlusion, it did not affect cyclic flow variations or time to reocclusion after thrombolysis.
Thapsigargin-Induced Calcium Entry and Apoptotic Death of Neutrophils Are Blocked by Activation of Protein Kinase C
Authors: Lucas Miguel , Díaz Pilar 
Published: April 2003

Intracellular free calcium ([Ca<sup>2+</sup>]<sub>i</sub>) concentration, free oxygen radical (FOR) production, DNA breakdown, and plasma membrane phosphorylation were studied in human neutrophils activated with thapsigargin and phorbol myrisate acetate (PMA). Thapsigargin produced a rapid and sustained rise of [Ca<sup>2+</sup>]<sub>i</sub>, activated the endonuclease, and caused the breakdown of the neutrophil’s DNA with a half-time close to 6 h. The protein kinase C activator PMA failed to inhibit the initial rise of [Ca<sup>2+</sup>]<sub>i</sub>, but inhibited the second phase of thapsigargin-induced calcium transient and completely blocked the activation of the endonuclease induced by thapsigargin. Thapsigargin induced a minor and delayed production of FOR, whereas PMA caused an abrupt and sustained FOR production that was enhanced by thapsigargin. Two plasma membrane proteins close to 50 and 64 kD were phosphorylated in PMA-activated neutrophils. These results suggest that the nonphosphorylated form of the membrane protein permits basal and thapsigargin-induced calcium entry. Phosphorylation by PMA of plasma membrane protein inhibits calcium uptake in both resting and thapsigargin-activated neutrophils and contributes to the block of the activation of the apoptotic endonuclease.
Reduction of Submissive Behavior in Rats: A Test for Antidepressant Drug Activity
Authors: Malatynska Ewa , Goldenberg Rachel , Shuck Lucy , Haque Arif , Zamecki Paula , Crites Glenda , Schindler Nancy , Knapp Richard J. 
Published: April 2003

Randomly paired rats were food deprived overnight and placed in an apparatus compelling them to compete for a food reward. About half of these pairs developed a dominant-submissive relationship measured as a significant difference in time spent on the feeder by each rat. This relationship developed over a 2-week period and remained stable for at least the next 5 weeks. Treatment of the submissive subjects, for at least 2 weeks, with imipramine, desipramine, or fluoxetine (10 mg/kg) significantly reduced submissive behavior. The effect faded after cessation of treatment with desipramine. Fluoxetine was further tested at 2.5- and 5-mg/kg doses and showed a dose-dependent reduction of submissive behavior. Treatment of submissive rats with the anxiolytic diazepam (1 mg/kg) was ineffective. The prevalence of dominant-submissive relationships and the effect of desipramine and imipramine on submissive behavior were gender independent. The predictive, face, and construct validity of the behavioral test is discussed.
Effect of Rebamipide on Cell Death Induced by Combined Treatment of Mild Heat Shock and Quercetin in RGM-1 Cells: A Role for HSP70 Induction
Authors: Tsukimi Yasuhiro , Fujishita Teruaki , Nakajima Kenji , Okabe Susumu 
Published: April 2003

The mechanism by which rebamipide inhibits cell death induced by combined treatment of mild heat shock and quercetin in RGM-1 cells was examined. Cells were incubated at 42°C for 1 h with or without quercetin. Expression of HSP70 was detected by immunoblot analysis and cell viability was determined by the MTT method. Upon treatment of cells with heat shock in the presence of quercetin, cell viability was significantly decreased 24 h after heat shock, with strong inhibition of HSP70 expression. Rebamipide suppressed both cell death and a reduction in HSP70 induced by the combined treatment of heat shock and quercetin. The combination of heat shock and quercetin resulted in DNA fragmentation, but rebamipide managed to inhibit such fragmentation. The protective effect of rebamipide was eliminated by cycloheximide or actinomycin D. Based upon these findings, it was concluded that rebamipide inhibited cell death resulting from combined treatment of mild heat shock and quercetin. The protective action of rebamipide appears to be at least partially due to maintenance of the HSP70 level.
Regulation of Endothelin-1 Production in Deoxycorticosterone Acetate- Salt-Treated Endothelial Cells
Authors: Yu Wen-Jen , Tomlinson Brian , Cheng Juei-Tang 
Published: April 2003

The aim of this study was to investigate the direct effect of deoxycorticosterone acetate (DOCA) on the expression of endothelin-1 (ET-1) mRNA and production of ET-1 peptides in cultured bovine carotid endothelial cells (BCEC) and human umbilical vein endothelial cells (HUVEC). The mineralocorticoid, DOCA, was administered to BCEC and HUVEC with or without additional salt (200 mmol/l). The ET-1 mRNA was elevated to 150% and 180% after a 24-hour incubation with DOCA (5 µmol/l) in BCEC and HUVEC, respectively. Intracellular content of ET-1 peptides of BCEC and HUVEC was increased from 21.66 ± 0.3 to 23.64 ± 0.19 fmol/10<sup>5</sup> cells and from 8.38 ± 0.82 to 11.26 ± 0.91 fmol/10<sup>5</sup> cells, respectively, in the DOCA-conditioned medium. Also, DOCA treatment for 24 h increased the secretion of ET-1 peptide from 1.62 ± 0.17 to 5.33 ± 0.67 fmol/10<sup>5</sup> cells in BCEC and from 0.95 ± 0.08 to 3.56 ± 0.36 fmol/10<sup>5</sup> cells in HUVEC. In DOCA-salt-treated endothelium, regulation of ET-1 gene was similar to that with DOCA alone. The DOCA-induced increase in expression of ET-1 mRNA and the ET-1 peptide level were both diminished in dexamethasone (DEX, 10 nmol/l)- or mifepristone (RU486, 0.5 µmol/l)-treated endothelium. These results suggest that DOCA directly increased the ET-1 mRNA expression in endothelium and could be mediated in part by a glucocorticoid receptor pathway which was independent of salt and hyperosmolarity.
An X-Ray Investigation of Pharyngeal Constriction in American English Schwa
Authors: Gick Bryan 
Published: April 2003

Abstract
A study of early X-ray footage of 4 subjects was conducted to test the prediction that there may be a midpharyngeal constriction in American English schwa. Results show a significant constriction during schwa relative to lingual rest position for all 4 speakers. This evidence contradicts views of American English schwa as having no articulatory target or place features, as well as those which have suggested a neutral target throughout the vocal tract. These findings, however, support claims connecting English schwa with reduced /r/. In addition to the basic effect 1 subject showed a bimodal pattern in schwa, which may indicate that this subject has distinct schwas in lexical vs. functional words, a property that has also been observed with respect to /r/ in r-vocalizing dialects.
Comparison of the Effectiveness of Some Pleural Sclerosing Agents Used for Control of Effusions in Malignant Pleural Mesothelioma: A Review of 117 Cases
Authors: Şenyiğit Abdurrahman , Bayram Hasan , Babayiğit Cenk , Topçu Füsun , Balci Akın E. , Satici Ömer 
Published: April 2003

<i>Background and Objectives: </i>Management of malignant pleural mesothelioma (MPM) has been an important clinical issue regardless of the treatment modality employed. We aimed to investigate the efficacy of oxytetracycline (OT), <i>Corynebacterium parvum</i> (CP), and nitrogen mustard (NM) in the management of pleural effusion associated with MPM. <i>Methods: </i>One hundred and seventeen patients who had stage-2 MPM or over according to the Butchart staging system and unilateral or bilateral pleural effusion took part in the study. The patients received either OT (35 mg/kg), CP (7 mg), or NM (0.4 mg/kg) through a chest tube for pleurodesis. The association between several clinical parameters and patient survival was also investigated. <i>Results: </i>OT was applied to 59, CP to 29 and NM to 29 cases. A statistical analysis of the results obtained by these agents have demonstrated that OT (30 days, 81%; 90 days, 76.2%) and CP (30 days, 86.2%; 90 days, 79.3%) led to a significantly higher rate of successful pleurodesis as compared to NM (30 days, 48.2%; 90 days, 41.3%; p <0.05). Although the procedure was generally well tolerated by the patients, the NM-treated group experienced significantly more nausea-vomiting (46.1%) and hypotension (35.8%) compared to patients who received OT (nausea-vomiting and hypotension 4.3%; p < 0.001) and CP (nausea-vomiting and hypotension 5.1%; p < 0.001). Furthermore, we found that thrombocytosis, chest pain and weight loss were significantly associated with poor prognosis, whereas epithelial type had a positive effect on survival. <i>Conclusion:</i> These results suggest that OT and CP may be used as effective sclerosing agents for pleurodesis in the control of pleural effusions associated with MPM, without major side effects.
Delivery of Fenoterol via Respimat<sup>®</sup>, a Novel ‘Soft Mist’ Inhaler
Authors: van Noord Jan A. , Smeets Joseph J. , Creemers Jacques P.H.M. , Greefhorst Louis P.M. , Dewberry Helen , Cornelissen Piet J.G. 
Published: April 2003

<i>Background:</i> The phase-out of chlorofluorocarbons (CFCs) for metered dose inhalers (MDIs) has prompted the development of alternative propellants and the design of propellant-free devices for inhalation therapy. <i>Objective:</i> This study was carried out to determine the dose of fenoterol inhaled from Respimat<sup>®</sup> (RMT), a new propellant-free soft mist inhaler, which is equivalent in terms of efficacy and safety to 1 puff of either 100 or 200 µg fenoterol inhaled from a conventional CFC-MDI (Berotec<sup>®</sup>). <i>Methods:</i> Sixty-two asthmatic patients (35 male, 27 female) with a mean baseline FEV<sub>1</sub> of 1.7 liters, corresponding to 55% of the predicted normal value, were randomized at two study centers to 4 of a total of 8 possible treatments: placebo; 12.5, 25, 50, 100, or 200 µg fenoterol via RMT, and 100 or 200 µg fenoterol delivered via the MDI. <i>Results:</i> Fifty-nine patients completed the study as planned. Results of the therapeutic equivalence test for the primary endpoint, average FEV<sub>1</sub> (AUC<sub>0–6</sub>)/6 and for the secondary endpoint, peak FEV<sub>1</sub>, showed that the 12.5- and 25-µg fenoterol doses administered via RMT were equivalent to the 100 µg fenoterol dose from the MDI. The 50-, 100- and 200-µg fenoterol doses delivered by RMT did not meet the criterion for therapeutic equivalence with the 100-µg dose from the MDI, and if tested for a difference would have been significantly different in favor of RMT. All 5 RMT fenoterol doses were therapeutically equivalent to the MDI 200-µg fenoterol dose. Headache, reported by 4 patients on test days and 2 patients between test days in those randomized to RMT, was the most common adverse event, but the active treatments were generally well tolerated with no dose-dependent increases in incidence or severity of adverse events observed. <i>Conclusions:</i> The results from the study suggest that safe and efficacious bronchodilation can be obtained from single-dose fenoterol administered via RMT. Use of lower absolute doses to obtain a clinically significant improvement in pulmonary function may be possible because of the increased lung deposition achievable with the novel soft mist inhaler.
Late-Onset Congenital Cystic Adenomatoid Malformation of the Lung
Authors: Luján Manel , Bosque Montserrat , Mirapeix Rosa M. , Marco M. Teresa , Asensio Oscar , Domingo Christian 
Published: April 2003

<i>Background:</i> Congenital cystic adenomatoid malformation of the lung (CCAM) is an embryonic developmental anomaly of an unknown etiology usually diagnosed antenatally by imaging techniques. A minority of cases may not be identified by prenatal imaging techniques and may go unnoticed for the first 6 months of their extrauterine life. Due to its rarity, physicians are unlikely to suspect the condition. <i>Objectives: </i>To highlight the embryology, clinical symptomatology, diagnostic procedures, therapeutic approach and clinical follow-up of a series of 12 patients with late-onset CCAM. <i>Methods:</i> An observational study which offers the description of the clinical presentation, diagnostic methods, treatment and follow-up of 12 patients with late-onset CCAM. Setting: A 600-bed teaching hospital in a reference area of 350,000 inhabitants. Patients: 12 patients from 1983 to 1999. <i>Results:</i> Twelve diagnosed cases of late-onset CCAM. Mean age at diagnosis: 6.7 years (range: 6 months to 23 years). Clinical presentation: 9 out of 12 (75%) with repeated lung infections, 2 out of 12 (16%) chance finding, and 1 case (8%) with pneumothorax. On pathological examination, 7 were found to be CCAM type I and 4 CCAM type II according to Stocker’s classification; 1 patient is currently awaiting surgery. The diagnostic method of choice nowadays is a computed tomography (CT) scan performed in the 7 more recent cases; in the former 5 cases an isotopic lung scan was done (and in 2 of them a bronchography was also performed). Treatment: 11 patients were operated: 8 lobectomies, 2 segmentectomies and 1 localized resection. Mean follow-up: 8 years (range: 6 months to 16 years). Complications: One reintervention due to a reappearance of the lesion in the patient who underwent localized resection of the CCAM. No cases of malignancy were found. <i>Conclusions:</i> Late-onset CCAM is an infrequent illness which requires a high level of clinical suspicion. It usually presents in the form of repeated infections. The most frequent pathological forms are type I and II (Stocker). The diagnostic method of choice is the CT scan. The recommended treatment is radical surgery of the lesion once diagnosis has been established. Malignancy and relapses are very infrequent when radical surgery is not postponed.
Metabolism of Prednisolone 21-Acetate in Hairless Mouse Skin
Authors: Hikima Tomohiro , Ohno Yasuo , Maibach Howard I. 
Published: April 2003

We investigated the hydrolytic activity of prednisolone 21-acetate (PNA) to prednisolone (PN) in an enzyme solution composed of esterase and skin homogenates from hairless mice. The values of the Michaelis-Menten constant obtained from hairless mouse skin and esterase solution were 14.2 and 10.2 µ<i>M</i>, respectively; conversely, the value of the maximum rate from hairless mouse and esterase solution were 0.67 and 1,886 nmol/min/mg protein, respectively. To examine the effect of enzymatic inhibitors on hydrolytic activity, five enzymatic inhibitors, 3,4-dichloroisocoumarine (DCIC), N-tosyl-<i>L</i>-phenylalanine chloromethyl ketone, iodoacetamide, <i>p</i>-hydroxymercuribenzoic acid (HMBA) and sodium dodecylsulfate, were added to the enzyme solution. Sixty-eight percent of hydrolytic activity in skin homogenates were not deactivated by DCIC which completely inhibited the enzymatic activity in esterase solution. We also studied the localization of hydrolytic enzyme with a subcellular faction: 66 and 11% of specific activity existed in microsome (Ms) and cytosol (Cp) fractions, indicating that the hydrolytic activity of PNA was included mainly in the Ms fraction. Hydrolytic activity in Ms and Cp fractions was different from sensitivity to enzymatic inhibitor; DCIC inhibited activity in the Ms fraction and, on the other hand, HMBA inhibited it in the Cp fraction. Therefore, Ms and Cp fractions in skin homogenates include a different esterase isoform and the metabolism of PNA to PN in hairless mouse skin is mediated by these isoforms.
The Role of Follicular Penetration
Authors: Schaefer H. , Lademann J. 
Published: April 2003

Textbooks describe percutaneous absorption through normal skin as diffusion through the stratum corneum barrier, i.e., in a simplified view, as a physiochemical interaction of a penetrating compound with the horizontal multilayer lipid structures and the underlying corneocytes within the horny layer. Hair follicles and sweat glands are vertical structures and are considered of little importance since ‘they represent a small and insignificant percentage of the skin surface’. To this integral view, a differentiated hypothesis is proposed: the more perfect the barrier function of the horny layer, the greater the relative role of the imperfections within the skin as a defence organ. Three kinds of imperfections should be taken into account: (1) the follicular apparatus of hair follicles; (2) the sweat glands, and (3) microlesions in the interfollicular horny layer. Each of these can theoretically represent a vertical pathway for percutaneous absorption, i.e. a ‘shunt’.