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Biomedical subjects

C Han

Publications and source records attributed to C Han.

At least 145 records · Page 8Linked to original sources
PubMed1994

Correlation of the response to nitroglycerin in rabbit aorta with the activity of the mu class glutathione S-transferase.

The relationship between the activity of glutathione S-transferases (GSTs), especially the mu isozyme, and the production of responses to nitroglycerin (GTN) was investigated in rabbit aorta. GST mu isozyme activity was measured using trans-stilbene oxide (TSO) as a substrate. Each aorta was divided into four parts, two of which were frozen for enzymatic analyses while the remaining two were used to measure the effects of GTN (0.5 microM), i.e. the increase in cGMP levels and the corresponding relaxation. Thus, all three measures were obtained in each individual rabbit aorta. Eight different rabbits were studied. An excellent correlation was obtained between the rise in cGMP and the mu isozyme activity (r2 = 0.948). A good correlation was also obtained between TSO activity and the relaxation response to GTN. Total GST activity did not correlate well with either cGMP increases or percent relaxation. These observations indicate that the activity of the mu isozyme measured using TSO and not the total GST correlates with the responses to GTN in the in vitro rabbit aorta model.

Animals↗
PubMed1994

Role of K+ channels in neuropeptide Y-induced vasoconstriction in rabbit cerebral basilar artery.

The role of K+ channels in the direct vasoconstrictive response induced by neuropeptide Y was investigated in isolated basilar arteries of rabbits and in vivo in rats. K+ channel openers, either BRL38227 or diazoxide, caused dose-dependent and complete relaxation of isolated arteries precontracted by neuropeptide Y. Exposure to both BRL38227 and diazoxide shifted the concentration-response curves for neuropeptide Y to the right without changing the maximal response. However, BRL38227 antagonized the angiotensin II-induced vasoconstriction noncompetitively. In vivo, the pressor responses produced by neuropeptide Y were significantly inhibited by pretreatment with BRL38227 in anesthetized rats. These results show that K+ channel openers antagonize neuropeptide Y-induced vasoconstriction in a competitive manner and suggest that blockade of K+ channels contributes, at least in part, to the direct vasoconstrictive effect of neuropeptide Y.

Animals↗
PubMed1994

Role of alpha 1A- and alpha 1B-adrenoceptors in phenylephrine-induced positive inotropic response in isolated rat left atrium.

We determined the distribution of alpha 1A- and alpha 1B-adrenoceptor subtypes and their functional roles in phenylephrine (PE)-induced positive inotropic responses in rat atrium. Radioligand binding assays in membrane preparations of rat atria showed that 62% of [125I]BE 2254 binding sites were irreversibly inactivated by pretreatment with 20 microM chloroethylclonidine (CEC). Inhibition curves for WB 4101 and 5-methyl-urapidil (5-MU) were better fit by a two-site model, comprising 29-35% high-affinity sites and 65-71% low-affinity sites, suggesting that rat atria contains both alpha 1A and alpha 1B subtypes in a ratio of approximately 1:2. In isolated perfused atria, pretreatment with CEC inhibited the maximum PE-induced positive inotropic response by 55%, and pA2 values for WB 4101 and 5-MU in inhibiting this response were 8.26 +/- 0.4 and 7.85 +/- 0.07, respectively, between the KD values for alpha 1A and alpha 1B subtypes. PE shifted the concentration-contractile response curve for Ca2+ to the left and upward. Pretreatment with CEC completely abolished whereas 1 nM WB 4101 did not alter, the effect of PE on Ca2+ sensitivity. These results demonstrate that both alpha 1A- and alpha 1B- adrenoceptor subtypes are involved in the PE-induced positive inotropic response. Only activation of the alpha 1B subtype potentiates the positive inotropic effect induced by increasing extracellular Ca2+, however, which suggests that the mechanisms involved in the action of the two subtypes may differ at least in part.

Adrenergic alpha-Antagonists↗
PubMed1994

[A study on alcohol drinking pattern in freshmen and sophomores].

Alcohol drinking pattern in 871 freshmen and sophomores of Han nationality was studied. Results showed 92.7% of the male and 72.9% of the female students were alcohol drinkers. There were highly significant differences in alcohol drinking pattern and types of alcoholic beverage they drank between males and females (P < 0.0001), and between students specializing in different subjects (P < 0.01). Alcohol drinking pattern of male students was influenced by their academic concerns and the drinking behavior of their fathers and friends.

Adult↗
PubMed1994

Selectivity of agonists for cloned alpha 1-adrenergic receptor subtypes.

The potencies and intrinsic activities of agonists in activating cloned alpha 1-adrenergic receptor (AR) subtypes were compared. The hamster alpha 1B-, bovine alpha 1C-, or rat alpha 1A/D-ARs were expressed at high levels in human embryonic kidney 293 cells. Catecholamines and phenylethylamines, but not lower efficacy agonists, were more potent in inhibiting radioligand binding to the expressed alpha 1A/D subtype than to the alpha 1B or alpha 1C subtypes; this selectivity remained in the presence of different buffers, nucleotides, and cations. Activation of all three subtypes caused substantial increases in [3H]inositol phosphate formation in cells grown in 96-well plates. Pretreatment with phenoxybenzamine decreased maximal responses to norepinephrine (NE) with only small decreases in apparent potency, suggesting similar small receptor reserves for all three subtypes. The catecholamines NE, epinephrine, and 6-fluoro-NE were full agonists with similar potencies at the three subtypes; alpha-methyl-NE was also a full agonist but was about 20-fold less potent at alpha 1B-ARs than at alpha 1C- or alpha 1A/D-ARs. Phenylephrine had similar potencies at all three subtypes but gave a submaximal response at alpha 1B-ARs. Methoxamine was a full agonist at alpha 1C- and alpha 1A/D-ARs, with about 20-fold greater potency at the alpha 1C subtype, but showed lower intrinsic activity at alpha 1B-ARs. A number of imidazolines, amidephrine, and SKF 89748 had substantial intrinsic activity at alpha 1C-ARs but little or no intrinsic activity at the other two subtypes. We conclude that the potencies of many agonists in competing for radioligand binding sites are related to their potencies in activating functional responses but that this relationship is not the same for all subtypes. NE and epinephrine activate all three cloned alpha 1-AR subtypes with similar potencies and intrinsic activities, but many widely used agonists show significant selectivity for different alpha 1-AR subtypes.

Adrenergic alpha-1 Receptor Agonists↗
PubMed1993

The inhibitory effect of Chinese tea and its polyphenols on in vitro and in vivo N-nitrosation.

The objective of this study is to evaluate the possible role of Chinese tea as a natural inhibitor of N-nitrosation, and to compare the relative inhibitory potency of various kinds of Chinese tea in vitro and in vivo. Studies on the inhibitory effect of 145 samples of Chinese tea on the formation of N-nitrosomorpholine (NMOR) showed that the inhibitory potency of the 7 types of Chinese tea differed greatly, the average blocking rate of green tea (89.04%, n = 60), crush, tear, and curl (CTC) black tea (86.99%, n = 13), brick tea (85.40%, n = 7), jasmine tea (84.99%, n = 21), Oolong tea (82.37%, n = 9), sun-dried tea (61.99%, n = 13) and Chinese Gongfu black tea (54.98%, n = 22), were positively correlated with their polyphenols contents. The inhibitory effect of green tea and black tea on endogenous N-nitrosation was also confirmed in 3 human volunteer experiments. Drinking tea after meal had a greater effect than drinking it before meal. It is concluded that Chinese tea can exert a relatively strong inhibitory potency for N-Nitroso compounds (NOC) formation both in vitro and in humans, and the active constituents may be related to their polyphenols contents, especially the tea catechin derivatives. The results also demonstrated that the amounts of NMOR formed in vitro depended on the molecular structure of tea catechin derivatives and their molar ratios to nitrite.

Adult↗
PubMed1993

Comparison of alpha 1-adrenergic receptor subtypes and signal transduction in SK-N-MC and NB41A3 neuronal cell lines.

We compared the alpha 1-adrenergic receptor subtypes in two neuronal cell lines, SK-N-MC (human neuroepithelioma) and NB41A3 (murine neuroblastoma). 125I-BE 2254 labeled alpha 1-adrenergic receptor binding sites in membranes from both cell lines. Pretreatment with the alpha 1B-selective alkylating agent chloroethylclonidine (CEC) completely eliminated these binding sites in NB41A3 cells but caused only a 50% loss in SK-N-MC cells. Displacement with subtype-selective antagonists suggested that NB41A3 cells express only the alpha 1B subtype, whereas SK-N-MC cells express a pharmacologically heterogeneous receptor population, including both alpha 1A and alpha 1B subtypes. Norepinephrine increased [3H] inositol phosphate formation in both cell lines, but with different sensitivities to pertussis toxin and the presence of extracellular Ca2+. CEC pretreatment eliminated this response in NB41A3 cells but caused a maximal 42% reduction in SK-N-MC cells. Use of subtype-selective antagonists showed that the [3H]inositol phosphate response involved only the alpha 1B subtype in NB41A3 cells but a combination of subtypes in SK-N-MC cells. Norepinephrine induced both transient and sustained increases in intracellular Ca2+ concentrations in both cell lines, as measured with fura-2. CEC pretreatment abolished the Ca2+ response in NB41A3 cells but had little effect in SK-N-MC cells. In SK-N-MC cells the Ca2+ response was potently blocked by alpha 1A-selective antagonists. Chelation of extracellular Ca2+ eliminated the sustained component of the Ca2+ signal in both cell lines. Poly(A)+ RNA from NB41A3, DDT1MF-2, BC3H1, and MDCK-D1 cell lines showed one or more prominent transcripts (2.2-4.2 kilobases) that strongly hybridized to the hamster alpha 1B cDNA probe but not to the bovine alpha 1C or rat alpha 1D cDNA probes. Poly(A)+ RNA from SK-N-MC cells showed multiple transcripts (1.3-5.6 kilobases) that hybridized to both hamster alpha 1B and rat alpha 1D but not bovine alpha 1C cDNA probes. We conclude that NB41A3 cells contain exclusively alpha 1B-adrenergic receptors linked to inositol phosphate formation and mobilization of intracellular Ca2+, whereas at least two alpha 1-adrenergic receptor forms, which resemble the alpha 1A and alpha 1B subtypes, coexist in SK-N-MC cells. The CEC-insensitive alpha 1A-like subtype in SK-N-MC cells is capable of increasing inositol phosphate formation and mobilizing intracellular Ca2+.

Animals↗
PubMed1992

Improved gas chromatographic assay for the simultaneous determination of nitroglycerin and its mono- and dinitrate metabolites.

A sensitive, specific capillary gas chromatographic-electron-capture detection method for the simultaneous determination of nitroglycerin (GTN), 1,2- and 1,3-glyceryl dinitrate (1,2-GDN and 1,3-GDN, respectively) and 1- and 2-glyceryl mononitrate (1-GMN and 2-GMN, respectively) is reported. The minimum quantifiable concentration for GTN, GDNs and GMNs is 0.4 ng/ml in plasma, with extraction recoveries for GMNs greater than 76% and for GTN and the GDNs greater than 95%. Over the full range of quantifiable concentrations the inter-run assay precision and accuracy were less than 13 and 11%, respectively, for all five nitrates. Similar intra-run assay precision and accuracy values were found. The method was employed in the preliminary in vitro examination of GTN, GDN and GMN kinetics in human blood. Following addition of GTN to human blood, the ratio of 1,2-GDN to 1.3-GDN maximum concentrations (Cmax) was ca. 7:1, reflecting preferential denitration of the GTN molecule at the primary positions, while the Cmax ratio for 2-GMN to 1-GMN in this system was ca. 6:1, representing a highly selective if not specific primary denitration of the 1,2-GDN molecule. Following the intravenous administration of 1,2-GDN to five healthy male volunteers, 2-GMN/1-GMN Cmax ratios averaged 8.8:1, representing a highly selective but not specific formation of 2-GMN from the 1,2-GDN molecule. The assay will find utility in in vitro studies attempting to address the molecular pharmacology of GTN and its metabolites, and in in vivo clinical pharmacology studies attempting to address the relationship between pharmacokinetics and pharmacodynamics of GTN and its metabolites.

Chromatography, Gas↗
PubMed1992

Inhibition of tobacco-specific nitrosamine-induced lung tumorigenesis in A/J mice by green tea and its major polyphenol as antioxidants.

In this study we examined the effects of green tea and its major components, (-)-epigallocatechin gallate (EGCG) and caffeine, on the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in A/J mice. We also studied the effects of green tea and EGCG on O6-methylguanine and 8-hydroxydeoxyguanosine (8-OH-dGuo) formation in lung tissues caused by NNK treatment. Mice were given 2% tea, 560 ppm EGCG, or 1120 ppm caffeine in drinking water for 13 weeks. During this time, NNK (11.65 mg/kg body weight) was administered by gavage three times weekly for 10 weeks from weeks 3 to 12. The bioassay was terminated 6 weeks after the last NNK treatment. Mice treated with NNK developed 22.5 lung adenomas per mouse, whereas NNK-treated mice that drank green tea or EGCG as drinking water developed only 12.2 (P less than 0.01) and 16.1 (P less than 0.05) tumors per mouse, respectively. Mice that drank green tea or caffeine solution showed lower body weight gains, although little difference in water and diet consumption was noted in these groups. While green tea and EGCG exerted little effect on the formation of O6-methylguanine, a critical DNA lesion in NNK lung tumorigenesis, both treatments suppressed the increase of 8-OH-dGuo levels in mouse lung DNA. The inhibition of 8-OH-dGuo formation in lung DNA by green tea and EGCG is consistent with their ability to inhibit lung tumorigenesis by NNK. Because 8-OH-dGuo is a DNA lesion caused by oxidative damage, these results suggest that the mechanism of inhibition by green tea and EGCG in NNK-induced lung tumorigenesis is due at least partly to their antioxidant properties.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1992

Subtypes of alpha 1-adrenoceptors in DDT1 MF-2 and BC3H-1 clonal cell lines.

We examined which subtype(s) of alpha 1-adrenoceptors are expressed in the widely used DDT1 MF-2 and BC3H-1 cell lines. Pretreatment with chloroethylclonidine (CEC) inactivated 76-85% of the specific [125I]BE 2254 binding sites in membrane preparations from both cell lines. Competition with subtype-selective competitive antagonists showed primarily the alpha 1B subtype in both cell lines. However, in BC3H-1 cells 5-methyl-urapidil showed complex behavior suggesting that about half of the binding sites had a lower affinity. Chloroethylclonidine pretreatment eliminated [3H]inositol phosphate responses to norepinephrine in both cell lines. Measurement of intracellular Ca2+ with fura-2 in DDT1 MF-2 cells showed that norepinephrine induced a complex response involving both transient and sustained components. Chloroethylclonidine pretreatment blocked both responses, while chelation of extracellular Ca2+ left the transient response intact but eliminated the sustained component. These results support previous work that these cell lines contain alpha 1B-adrenoceptors linked to inositol phosphate formation and mobilization of intracellular Ca2+. However, these results show that alpha 1B-adrenoceptors can be linked to Ca2+ influx as well as intracellular mobilization, and support the existence of pharmacologically distinct alpha 1B variants.

Adrenergic alpha-Antagonists↗
PubMed1992

Inhibition by germanium oxide of the mutagenicity of cadmium chloride in various genotoxicity assays.

The effects of germanium oxide on the genotoxicity of cadmium chloride were investigated. The incorporation of [3H]thymidine into testicular DNA was inhibited in mice injected ip with 1.35, 1.80 or 2.70 mg cadmium chloride/kg body weight. Germanium oxide (0.05 or 0.1 mg/kg body weight, sc) alone did not affect [3H]thymidine incorporation into testicular DNA but 0.05 mg germanium oxide/kg antagonized the inhibitory effect of 1.35 mg cadmium chloride/kg. However, combinations of the other doses of the two compounds did not show statistically significant antagonistic effects. Cadmium chloride significantly increased the frequencies of micronucleus formation in polychromatic erythrocytes, and of chromosome aberrations in the bone marrow of mice treated with 0.7, 1.4 or 2.7 mg/kg body weight, in a dose-related manner. These effects were inhibited by germanium oxide at doses of 0.1 or 0.5 mg/kg body weight, although germanium oxide alone did not affect micronucleus formation or the chromosome aberration rate. Cadmium chloride produced a dose-related increase in the frequency of sister chromatid exchanges in cultured human lymphocytes at concentrations of 5, 10 or 50 mumol. This effect was also inhibited by germanium oxide (0.05 or 0.1 mumol), although germanium oxide alone had no effect. There was a dose-related increase in the frequency of sperms with abnormal head morphologies from mice treated with 0.6, 1.1 or 2.2 mg cadmium chloride/kg body weight and this too was antagonized by the injection of germanium oxide (0.1 or 0.5 mg/kg body weight). Germanium oxide alone did not affect the frequency of sperm-head abnormalities.

Animals↗
PubMed1992

Lack of effects of selenium on N-nitrosomethylbenzylamine-induced tumorigenesis, DNA methylation, and oncogene expression in rats and mice.

The effects of dietary selenium deficiency and excess on N-nitrosomethylbenzylamine-(NMBA) induced esophageal neoplasia in rats and forestomach tumors in mice and the effects of dietary selenium on DNA adduct formation and on the activities of DNA adduct-repairing enzyme and oncogene expression in rat esophagus were investigated. The esophageal and forestomach tumors were induced by administration of NMBA by gavage with a total dose of 39 mg/kg body wt in rats and 12 mg/kg body wt in mice. Neither selenium dietary deficiency (Se < 0.02 ppm) nor selenium excess (2.0 ppm) showed any significant effect on the incidence of tumors or number of tumors per tumor-bearing animal. For the DNA adduct formation studies, rats were given a dose of NMBA intraperitoneally after six weeks on the different selenium-containing diets. No significant difference in the amount of the DNA adduct O6-methyldeoxyguanosine was found among the different selenium-treated groups. In a parallel group of rats that did not receive NMBA, the levels of esophageal O6-methyldeoxyguanosine DNA methyltransferase were not significantly altered by dietary selenium levels. The c-myc oncogene expression in rat esophagus was induced by the administration of NMBA (3 mg/kg body wt) by gavage once a week for eight weeks. Dietary selenium did not show any effects on its expression. On the basis of the results of these studies, dietary selenium has no effects in the NMBA-induced tumor model.

Animals↗
PubMed1992

Coexisting beta 1- and atypical beta-adrenergic receptors cause redundant increases in cyclic AMP in human neuroblastoma cells.

In SK-N-MC human neuroblastoma cells, the cAMP response to 10 nM isoproterenol (ISO) is mediated primarily by beta 1-adrenergic receptors. However, responses to higher concentrations of ISO (100-1000 nM) were only weakly blocked by beta 1- and beta 2-selective antagonists. When beta 1 receptors were blocked with 10 microM CGP 20712A, catecholamines still maximally activated cAMP accumulation, with only small decreases in potency. In the presence of CGP 20712A, beta blockers inhibited the response to ISO stereoselectively but with relatively low potencies. Pindolol derivatives were partial agonists with low potencies, and the atypical agonist BRL 37344 was a partial agonist with an intermediate potency. All binding sites in these cells labeled by 125I-cyanopindolol were of the beta 1 subtype. Nuclease protection assays indicated that SK-N-MC cells contain mRNA for both the human beta 1- and beta 3-adrenergic receptors, with the beta 3 subtype mRNA being expressed 25-50% more abundantly than that for the beta 1 subtype. Northern blot hybridizations showed the presence of two beta 3 mRNA transcripts of 3.1 and 2.4 kilobases. These results suggest that beta 1- and atypical beta-adrenergic receptors coexist in these cells and cause redundant increases in cAMP formation. Although molecular approaches suggest that the atypical subtype is the beta 3, the observed drug specificity differs from that reported for the expressed recombinant human beta 3 receptor.

Adrenergic beta-Agonists↗
PubMed1992

Calcitonin gene-related peptide (CGRP) and neuropeptide Y (NPY) levels are elevated in plasma and decreased in vena cava during endotoxin shock in the rat.

Calcitonin gene-related peptide (CGRP), a potent vasodilator, and neuropeptide Y (NPY), a potent vasoconstrictor and potentiator of norepinephrine-induced vasoconstriction, were examined in an animal model of endotoxin shock. Gram-negative bacterial endotoxin (lipopolysaccharide B from Salmonella enteritidis) was administered as a bolus (16.7 mg/kg, i.v.) to conscious, unrestrained rats, previously cannulated for blood pressure measurements and blood withdrawal. At 30 min, endotoxin caused 35-40 mm Hg drop in mean arterial pressure and significant increases in heart rate and plasma levels of glucose and lactate. By 3 hr, blood pressure had returned to near normal levels and remained normal until cardiovascular collapse at 4-6 hr (approximately 70% of the rats). Endotoxin elevated plasma CGRP levels by fourfold at 30 min and 22-fold at 3 hr. Of the organs tested, only vena cava showed significant decreases in CGRP levels. Endotoxin also elevated plasma NPY levels by 67% and decreased NPY levels in adrenal gland and vena cava at 30 min and 3 hr. The data suggest that both CGRP and NPY are released into the circulation during development of endotoxin shock in the rat. NPY may contribute to the compensatory mechanism, tending to bring arterial pressure back to normal levels during intermediate stages of endotoxemia. CGRP, because of its extremely high potency as a hypotensive agent, may contribute to the hypotension at both early and late stages during pathogenesis of endotoxin shock.

Animals↗