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C F Chen

Publications and source records attributed to C F Chen.

At least 109 records · Page 6Linked to original sources
PubMed1999

Effects of evodiamine on the secretion of testosterone in rat testicular interstitial cells.

Evodiamine, a bioactive component isolated from the Chinese medicine Wu-chu-yu, exhibits vasodilative and antianoxic action. Although evodiamine indeed has many biological effects, its effects on the endocrine system are not clear. The present study explored the effects of evodiamine on testosterone secretion in vitro. Rat collagenase-dispersed testicular interstitial cells (TICs) were incubated with evodiamine (0 to 10(-4) mol/L) in the presence or absence of human chorionic gonadotropin (hCG), forskolin, 8-bromo-adenosine 3':5'-cyclic monophosphate (8-Br-cAMP), or steroidogenic precursors (including 25-hydroxycholesterol, pregnenolone, progesterone, 17alpha-hydroxyprogesterone, and androstenedione) at 34 degrees C for 1 hour. The testosterone concentration in the media samples was measured by radioimmunoassay. Evodiamine 10(-4) mol/L was effective to reduce both basal and hCG-stimulated testosterone secretion in rat TICs after 1, 2, or 4 hours of incubation. The stimulatory effect of forskolin on testosterone release in TICs was prevented by administration of evodiamine. Evodiamine 10(-4) mol/L also decreased 8-Br-cAMP- and androstenedione-stimulated testosterone secretion. These results suggest that evodiamine reduces testosterone secretion in rat TICs via a mechanism involving reduced activity of cAMP-related pathways and 17beta-hydroxysteroid dehydrogenase (17beta-HSD).

Animals↗
PubMed1999

Effects of veratrine and paeoniflorin on the isolated rat aorta.

The interactions and mechanisms between veratrine and paeoniflorin on the isolated rat aorta were studied. Veratrine (1x10(-6) to 1x10(-4) g/ml) could induce contraction on the isolated rat aorta in a concentration-related manner. Paeoniflorin had no effect on the isolated rat aorta. Pretreatment with prazosin (1x10(-6) M) and nifedipine (1x10(-6) M) but not yohimbine (1x10(-5) M) could decrease the tension of contraction induced by veratrine (1x10(-4) g/ml). Sodium nitroprusside (1x10(-4) M) could inhibit the contraction induced by veratrine (1x10(-4) g/ml) with or without endothelium, whereas methylene blue (5x10(-5) M) could increase the contraction induced by veratrine (1x10(-4) g/ml). Treatment with veratrine (1x10(-4) g/ml) could decrease the tension of contraction induced by norepinephrine (1x10(-6) M) or phenylephrine (1x10(-4) M). The inhibition of veratrine on norepinephrine-induced contraction was potentiated by L-arginine (1x10(-4) M) and reversed by L-NAME (1x10(-5) M). Paeoniflorin (1x10(-4) M) could decrease the tension of contraction induced by veratrine (1x10(-4) g/ml) and methylene blue (5x10(-5) M). The inhibition of paeoniflorin on veratrine was more potent on rat isolated aorta with endothelium than without endothelium. Ryanodine (1x10(-5) M) and Ca2+ -free medium could inhibit methylene blue-induced contraction. From the above results, the relaxation of veratrine on the norepinephrine-induced contraction might be related to the increase of NO and cGMP. The contraction of veratrine on the isolated rat aorta was via the increase of intracellular calcium which was inhibited by paeoniflorin.

Animals↗
PubMed1999

Pharmacokinetic and pharmacodynamic analyses of trazodone in rat striatum by in vivo microdialysis.

The aim of this study was to investigate the brain pharmacokinetics and pharmacodynamics of trazodone. Sensitive microbore high-performance liquid chromatographic methods with electrochemical detection (LC-ED) were developed for the determination of trazodone, serotonin (5-HT), and their respective metabolites. The feasibility of microdialysis coupled with LC-ED system for direct analysis of these compounds in the rat striatum was investigated. Striatal dialysates were automatically injected onto a cyano microbore column, through an on-line injector, for the determination of trazodone and its metabolite or onto a reversed phase microbore column for the determination of 5-HT and its metabolite. A monophase phenomenon with a first-order elimination rate constant was observed for trazodone. The brain pharmacokinetics of trazodone appear to conform to a one-compartment model. Surprisingly, no significant changes in striatal 5-HT or its metabolite were observed following the same dosage and time course. The present results suggest that brain microdialysis methods may be applicable to pharmacokinetic and pharmacodynamic studies of psychotrophic agents.

Animals↗
PubMed1999

Nepalolide A inhibits the expression of inducible nitric oxide synthase by modulating the degradation of IkappaB-alpha and IkappaB-beta in C6 glioma cells and rat primary astrocytes.

1 The effects of nepalolide A on the expression of inducible nitric oxide synthase (iNOS) caused by incubation with lipopolysaccharide/interferon-gamma (LPS/IFN-gamma) or tumour necrosis factor-alpha/interleukin-1beta/IFN-gamma (TNF-alpha/IL-1beta/IFN-gamma, mixed cytokines) in C6 glioma cells and primary astrocytes of rat were investigated. The mechanisms by which nepalolide A confers its effect on iNOS expression were also elucidated. 2 Treatment with LPS/IFN-gamma and mixed cytokines for 24 h elicited the induction of iNOS activity as determined by nitrite accumulation in the culture medium and assay of enzyme activity. Nepalolide A at 10 microM abrogated the LPS/IFN-gamma- and mixed cytokines-mediated induction of iNOS by more than 90% in C6 glioma cells, and by 80% for mixed cytokines-induced induction of iNOS in primary astrocytes. The effect of nepalolide A (2-10 microM) was concentration-dependent. 3 The inhibition of iNOS induction by nepalolide A was attributed to decreases in the content of iNOS protein and the level of iNOS mRNA, as measured by immunoblotting and reverse transcriptase-polymerase chain reaction. 4 Electrophoretic mobility shift assay was used to evaluate the effect of nepalolide A on the activation of nuclear factor-kappaB (NF-kappaB). Results showed that nepalolide A diminished the LPS/IFN-gamma-mediated association of NF-kappaB with consensus oligonucleotide in a concentration-dependent manner. The activation of NF-kappaB by mixed cytokines was modulated both in the extent of activation and in its time-course by nepalolide A. 5 The ability of nepalolide A to inhibit NF-kappaB activation was further confirmed by studies on the degradation of the inhibitor of NF-kappaB, IkappaB, as measured by immunoblotting. 6 The present study demonstrates that the attenuation of NF-kappaB activation by nepalolide A was mediated by blockade of the degradation of IkappaB, leading to suppression of the expression of iNOS.

Animals↗
PubMed1999

Tetrandrine ameliorates ischaemia-reperfusion injury of rat myocardium through inhibition of neutrophil priming and activation.

1. We have previously shown that tetrandrine (TTD), a bisbenzyltetrahydroiosquinoline isolated from the Chinese herb Stephania tetrandra, inhibits neutrophil adhesion, Mac-1 expression, and reactive oxygen species (ROS) production. To examine whether inhibition of neutrophil function may confer upon TTD the ability to prevent myocardial ischaemia-reperfusion (MI/R) injury, experiments were performed on rats subjected to coronary ligation followed by reperfusion for induction of MI/R injury. 2. Intravenous administration of TTD (0.1 and 1.0 mg kg-1) 15 min prior to coronary ligation completely prevented MI/R-associated mortality. TTD pretreatment also significantly reduced MI/R-induced ventricular tachyarrhythmia, myocardial infarct size, and neutrophil infiltration. 3. However, TTD pretreatment did not influence mean arterial blood pressure, heart rate, or product of pressure-rate, indicating that TTD extenuated MI/R through mechanisms independent of modulating haemodynamics or myocardial oxygen demand. 4. Peripheral blood neutrophils were isolated for ex vivo examination of shape change and Mac-1 upregulation of neutrophils, two sensitive indicators of proinflammatory priming, as well as N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced adhesion and ROS production, parameters commonly used for the assessment of neutrophil activation. 5. Neutrophils from MI/R animals showed significant shape change and Mac-1 upregulation, both of which were prevented by TTD-pretreatments. On the other hand, fMLP-induced adhesion and ROS production of neutrophils were markedly enhanced by MI/R but diminished in TTD-pretreated animals. 6. These data suggest that the protective effect of TTD against MI/R injury can be accounted for by inhibition of neutrophil priming and activation, thereby abolishing subsequent infiltration and ROS production that cause MI/R injury.

Alkaloids↗
PubMed1999

Inhibition of activated human mesangial cell proliferation by the natural product of Cordyceps sinensis (H1-A): an implication for treatment of IgA mesangial nephropathy.

Cordyceps sinensis (CS) is a parasitic fungus that has been used as a Chinese medicine for a long time in the treatment of nephritis. Today, the hypothesis about the pathogenesis of immunoglobulin A nephropathy (IgAN) is that nephritogenic IgA immune complexes (IgAIC) go to the kidney to stimulate resting mesangial cells to release cytokines and growth factors. These cytokines and growth factors cause mesangial cell proliferation and release matrix, chemical mediators that lead to the glomerular injury. However, nephritogenic IgAIC in humans is still unknown. To solve this problem previously, we established an in vitro model that showed that cultured human mesangial cells (HMC) stimulated with interleukin-1 (IL-1) plus IL-6 can cause mesangial cell proliferation, increasing production of chemical mediators and superoxide anion. An in vivo model also proved that this culture medium may lead to renal injury with hematuria and proteinuria. Therefore, to fractionate the crude components that can be used in the treatment of patients with IgAN, we cultured HMC, and then an HMC activating model with HMC incubated with IL-1 and IL-6 was established. We fractionated the crude methanolic extracts from fruiting bodies of CS with the use of this in vitro inhibition of HMC activation model as our assay method. In brief, the fruiting bodies were extracted by silica gel column chromatography. One out of 6 column fractions, F-2, significantly inhibited the HMC activation by IL-1 plus IL-6. The acute toxicity test with male Institute of Cancer Research mice showed no liver toxicity or mutagenicity. Then we established an IgAN animal model with R36A (Pneumococcal C-polysaccharide purified from Streptococcus pneumoniae) as antigen and anti-R36A IgA monoclonal antibody to form nephritogenic IgA-IC, which can induce hematuria and proteinuria in mice with IgA deposition in the mesangial area. The mice in the IgAN model fed with 1% F-2 in diet had significant reduction of hematuria and proteinuria together with histopathologic improvement. Therefore this fraction was then purified by silica gel column chromatography and high-performance liquid chromatography, which got a purified compound H1-A, which can suppress the activated HMC and alleviate IgAN (Berger's disease) with clinical and histologic improvement. These results give us a new regimen for the treatment of patients with IgAN in the future.

Adolescent↗
PubMed1999

Suppression of inducible cyclooxygenase and inducible nitric oxide synthase by apigenin and related flavonoids in mouse macrophages.

Prostaglandins biosynthesis and nitric oxide production have been implicated in the process of carcinogenesis and inflammation. In this study, we investigated the effect of various flavonoids and (-)-epigallocatechin-3-gallate on the activities of inducible cyclooxygenase (COX-2) and inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. Apigenin, genistein and kaempferol were markedly active inhibitors of transcriptional activation of COX-2, with IC(50) < 15 microM. In addition, apigenin and kaempferol were also markedly active inhibitors of transcriptional activation of iNOS, with IC(50) < 15 microM. Of those compounds tested, apigenin was the most potent inhibitor of transcriptional activation of both COX-2 and iNOS. Western and northern blot analyses demonstrated that apigenin significantly blocked protein and mRNA expression of COX-2 and iNOS in LPS-activated macrophages. Transient transfection experiments showed that LPS caused an approximately 4-fold increase in both COX-2 and iNOS promoter activities, these increments were suppressed by apigenin. Moreover, electrophoretic mobility shift assay (EMSA) experiments indicated that apigenin blocked the LPS-induced activation of nuclear factor-kB (NF-kB). The inhibition of NF-kB activation occurs through the prevention of inhibitor kB (IkB) degradation. Transient transfection experiments also showed that apigenin inhibited NF-kB-dependent transcriptional activity. Finally, we showed that apigenin could inhibit the IkB kinase activity induced by LPS or interferon-gamma. The results of further studies suggest that suppression of transcriptional activation of COX-2 and iNOS by apigenin might mainly be mediated through inhibition of IkB kinase activity. This study suggests that modulation of COX-2 and iNOS by apigenin and related flavonoids may be important in the prevention of carcinogenesis and inflammation.

Animals↗
PubMed1999

Impediment to calcium influx and reactive oxygen production accounts for the inhibition of neutrophil Mac-1 Up-regulation and adhesion by tetrandrine.

We studied the mechanisms by which the plant alkaloid tetrandrine (TTD) inhibits Mac-1-dependent neutrophil adhesion to fibrinogen. TTD (0.1-10 microM) significantly inhibited Mac-1 up-regulation and neutrophil adhesion, as induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP) or phorbol-myristate-acetate (PMA). Treatment of neutrophils with fMLP or PMA caused a rapid influx of Ca++ and accumulation of reactive oxygen species (ROS), both of which have been shown to enhance neutrophil adhesion via Mac-1 up-regulation. Because TTD antagonizes Ca++ influx and abrogates ROS, we examined the relationship between Ca++ influx, ROS formation, and Mac-1 expression in TTD-inhibited neutrophil adhesion. TTD alone caused a slight but statistically significant increase in [Ca++]i with no effect on adhesion. In contrast, TTD as well as two Ca++ channel antagonists, verapamil and nifedipine, markedly diminished fMLP- and PMA-induced Ca++ influx, Mac-1 up-regulation, and adhesion. TTD also inhibited increases in [Ca++]i and adhesion induced by the ionophore A23187 but failed to inhibit those induced by thapsigargin, an agent mobilizing Ca++ from intracellular stores. Thus, TTD impeded Ca++ influx from outward to avert neutrophil adhesion. Similarly, TTD and two ROS scavengers, superoxide dismutase and catalase, abolished ROS production, Mac-1 up-regulation, and neutrophil adhesion. Ca++ and ROS, therefore, represent two essential signals for Mac-1 up-regulation upon fMLP or PMA stimulation. Our data suggest that the antiadherent effect of TTD is mediated, in part, by the inhibition of Ca++ influx and ROS formation, resulting in suppressed up-regulation of Mac-1 and, in turn, neutrophil adhesion to fibrinogen.

Adult↗
PubMed1999

Chronic activation of neurokinin-1 receptor induces pulmonary hypertension in rats.

In this study we explored the hypothesis that chronic activation of neurokinin-1 (NK-1) receptor induces pulmonary hypertension in Wistar rats. First, the activation of NK-1 receptor on the pulmonary circulation was investigated by use of a chronic injection of NK-1 agonist [Ser9,Met(O2)11]-substance P (1 x 10(-9) mol/kg) for 2 wk at sea level (rats breathed room air) and during hypoxia (rats were placed in a hypobaric 380-Torr chamber). Second, we studied the effect of NK-1 antagonist (CP-96345) on developing and developed (after 4 wk of chronic hypoxia) pulmonary hypertension. Pulmonary arterial pressure, the weight ratio of right ventricle to left ventricle + septum, hematocrit, and substance P (SP) were measured. We found that NK-1 agonist significantly increased pulmonary arterial pressure in the sea-level but not in the hypoxic group. However, NK-1 agonist induced neither right heart hypertrophy nor polycythemia. CP-96345 significantly decreased pulmonary arterial pressure in the hypoxic group but had no effect in the sea-level group. Furthermore, CP-96345 significantly attenuated the acute SP-induced increase in pulmonary arterial pressure in the sea-level and hypoxic groups, with a larger increase in the hypoxic group. These results suggest that chronic activation of NK-1 receptor induces pulmonary hypertension and that there is an increase in the sensitivity of pulmonary vessels in response to SP in chronically hypoxic rats.

Animals↗
PubMed1999

Effect of aging on gender differences in neural control of heart rate.

To clarify the influence of gender on sympathetic and parasympathetic control of heart rate in middle-aged subjects and on the subsequent aging process, heart rate variability (HRV) was studied in normal populations of women (n = 598) and men (n = 472) ranging in age from 40 to 79 yr. These groups were divided into eight age strata at 5-yr intervals and were clinically diagnosed as having no hypertension, hypotension, diabetic neuropathy, or cardiac arrhythmia. Frequency-domain analysis of short-term, stationary R-R intervals was performed, which reveals very-low-frequency power (VLF; 0.003-0.04 Hz), low-frequency power (LF; 0.04-0.15 Hz), high-frequency power (HF; 0.15-0.40 Hz), the ratio of LF to HF (LF/HF), and LF and HF power in normalized units (LF% and HF%, respectively). The distribution of variance, VLF, LF, HF, and LF/HF exhibited acute skewness, which was adjusted by natural logarithmic transformation. Women had higher HF in the age strata from 40 to 49 yr, whereas men had higher LF% and LF/HF between 40 and 59 yr. No disparity in HRV measurements was found between the sexes in age strata >/=60 yr. Although absolute measurements of HRV (variance, VLF, LF, and HF) decreased linearly with age, no significant change in relative measurements (LF/HF, LF%, and HF%), especially in men, was detected until age 60 yr. We conclude that middle-aged women and men have a more dominant parasympathetic and sympathetic regulation of heart rate, respectively. The gender-related difference in parasympathetic regulation diminishes after age 50 yr, whereas a significant time delay for the disappearance of sympathetic dominance occurs in men.

Adult↗
PubMed1999

Microdialysis study of biliary excretion of chloramphenicol and its glucuronide in the rat.

The biliary excretion of chloramphenicol and its glucuronide has been evaluated by use of a microdialysis probe linked to automatic on-line microbore high-performance liquid chromatography. The microdialysis probe was inserted into the bile duct between the liver and the duodenum; to avoid obstruction of the bile duct or bile salt waste, a shunt linear probe was used. After intravenous administration of chloramphenicol succinate (100 mg kg(-1)) the amounts of unbound chloramphenicol and its glucuronide in the bile microdialysate were recorded. According to the pharmacokinetic results disposition of chloramphenicol seems to fit a two-compartment model whereas that of chloramphenicol glucuronide fits a one-compartment model in rat bile. The area under the concentration-time curve for chloramphenicol glucuronide was twice that for chloramphenicol in rat bile duct. Clearance of chloramphenicol glucuronide was significantly higher than that of chloramphenicol in biliary excretion, indicating that chloramphenicol and its glucuronide are actively excreted into the bile.

Animals↗
PubMed1999

Rheologic determinant changes of erythrocytes in Binswanger's disease.

BACKGROUND: Binswanger's disease (BD) has been associated with severe arteriosclerotic changes in the long perforating arteries and with impaired cerebrovascular responsiveness to hypercapnia. Rheology parameters may become important factors in regulating cerebral blood flow. The purpose of this study was to investigate the changes in rheologic determinants of erythrocytes and to discuss the relation of erythrocytes and white matter lesions in this type of dementia. METHODS: Twenty-eight patients suffering from BD and a control group matched for age, sex and cerebrovascular risk factors were tested for the following hemorheologic variables: erythrocyte deformability, erythrocyte membrane fluidity, erythrocyte aggregation, plasma viscosity and whole blood viscosity. Additionally, red cell membrane metabolic parameters, lipids and individual membrane phospholipids, sialic acid (SA) and malondialdehyde (MDA) contents, and ATPase activities were measured. RESULTS: A significant decrease in erythrocyte deformability, erythrocyte membrane fluidity, membrane phosphatidylethanolamine, membrane phosphatidylcholine, membrane SA and membrane ATPase activities, and a significant increase in membrane cholesterol, cholesterol to total phospholipid ratio, MDA, broad viscosity and erythrocyte aggregation were observed in BD patients when compared with those of the matched control group. CONCLUSIONS: Changes in erythrocyte membrane parameters, especially in phospholipids, can produce serious metabolic disorders and influence the rheologic properties of erythrocytes in patients with BD. These alterations can contribute to a circulatory slowdown and may lead to worsening of the condition of the cerebral white matter in these patients.

Adenosine Triphosphatases↗
PubMed1999

Vasorelaxing action of rutaecarpine: effects of rutaecarpine on calcium channel activities in vascular endothelial and smooth muscle cells.

Rutaecarpine (Rut) has been shown to induce hypotension and vasorelaxation. In vitro studies indicated that the vasorelaxant effect of Rut was largely endothelium-dependent. We previously reported that Rut increased intracellular Ca2+ concentrations ([Ca2+]i) in cultured rat endothelial cells (ECs) and decreased [Ca2+]i in cultured rat vascular smooth muscle (VSMCs) cells. The present results showed that the hypotensive effect of Rut (10-100 microgram/kg i.v.) was significantly blocked by the nitric oxide synthase inhibitor Nomega-nitro-L-arginine. In aortic rings, Rut (0. 1-3.0 microM)-induced vasorelaxation was inhibited by Nomega-nitro-L-arginine and hydroquinone but not by antagonists of the various K+ channels, 4-aminopyridine, apamin, charybdotoxin, or glibenclamide. Rut (0.1 and 1.0 microM) inhibited the norepinephrine-induced contraction generated by Ca2+ influx and at 1.0 microM increased cyclic GMP (cGMP) production in endothelium-intact rings and to a lesser extent in endothelium-denuded rings. In whole-cell patch-clamp recording, nonvoltage-dependent Ca2+ channels were recorded in ECs and Rut (0.1, 1.0 microM) elicited an opening of such channels. However, in VSMCs, Rut (10.0 microM) inhibited significantly the L-type voltage-dependent Ca2+ channels. In ECs cells, Rut (1.0, 10.0 microM) increased nitric oxide release in a Ca2+-dependent manner. Taken together, the results suggested that Rut lowered blood pressure by mainly activating the endothelial Ca2+-nitric oxide-cGMP pathway to reduce smooth muscle tone. Although the contribution seemed to be minor in nature, inhibition of contractile response in VSMCs, as evidenced by inhibition of Ca2+ currents, was also involved. Potassium channels, on the other hand, had no apparent roles.

4-Aminopyridine↗
PubMed1999

Effects of norepinephrine on renal function in chronically hypoxic rats.

The sympathetic nervous system is activated in response to altitude hypoxia and activation of renal sympathetic nerves may cause vasoconstriction and fluid retention. However, renal excretion does not differ significantly between rats exposed to high altitude hypoxia and control rats. We hypothesize that renal response to norepinephrine (NE) is altered after chronic hypoxia. Female Wistar rats weighing 200 to 220 g were exposed to hypoxia in an altitude chamber (5,500 m, 380 torr) 15 hours/day for 4 weeks (HA, high altitude). Our findings showed that systemic infusion of NE (300 micrograms.kg-1.hr-1) produced less diuresis/natriuresis in HA rats that in sea level (SL) controls. With mechanical elevation of arterial blood pressure, both SL and HA rats showed no significant difference in their response to pressure diuresis. Direct intrarenal arterial NE (10 micrograms.kg-1.hr-1) administration reduced renal function more in HA rats than in SL rats. Intrarenal arterial administration of L-arginine (100 micrograms.kg-1.hr-1) did not alter the renal action of NE in HA rats. However, with intrarenal arterial infusion of phosphoramidon (100 micrograms.kg-1.hr-1), NE increased renal response in HA rats to almost the same level as that in SL rats. These results suggest that HA rats may have either an excess renal action of antidiuretic and antinatriuretic factors or an insufficient renal action of diuretic and natriuretic factors during NE administration.

Altitude↗