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Biomedical subjects

S X Liu

Publications and source records attributed to S X Liu.

At least 55 records · Page 3Linked to original sources
PubMed1997

Circulating transforming growth factor beta 1 and coronary artery disease.

OBJECTIVE: Transforming growth factor beta 1 (TGF-beta 1), a multifunctional cytokine, is involved in many physiological and pathological processes and possibly in atherogenesis. METHODS: We explored the association between circulating plasma TGF-beta 1 measured by ELISA and coronary artery disease (CAD) assessed angiographically in 371 Caucasian patients (269 men and 102 women) aged < or = 65 years. RESULTS: While mean +/- s.e.m total TGF-beta 1 was not different among patients with (56.9 +/- 1.5 ng/ml) or without (54.6 +/- 2.8 ng/ml) angiographically demonstrable CAD, naturally active TGF-beta 1 was significantly higher in CAD patients (1.74 +/- 0.18 vs 0.96 +/- 0.17 ng/ml, P < 0.01). Active TGF-beta 1 increased with the number of major coronary arteries with more than 50% luminal obstruction (P < 0.01) and patients with triple vessel disease had twice the level of those with no or mild vessel disease (2.15 +/- 0.46 vs 1.12 +/- 0.14 ng/ml, P < 0.001). We found no relationship between TGF-beta 1 and Lp(a), but TGF-beta 1 was significantly correlated with circulating fibrinogen (r = 0.178, P = 0.005) and fasting glucose (r = 0.177, P = 0.007) levels. CONCLUSIONS: Our study identifies an increase in active TGF-beta 1 levels with both the occurrence and severity of CAD which is independent of standard CAD risk factors. This may reflect a 'double-edged sword' effect of TGF-beta 1 in that it may reduce atherogenesis by inhibiting smooth muscle cell proliferation but, when there is ongoing vessel wall injury, enhance it by promoting excessive extracellular matrix accumulation. The outcome could represent a complex balance between these two competing influences.

Aged↗
PubMed1997

Nitric oxide donors: effects of S-nitrosoglutathione and 4-phenyl-3-furoxancarbonitrile on ocular blood flow and retinal function recovery.

It is known that NO is involved in the regulation of intraocular pressure (IOP) and retinal function recovery after ischemia. Thus, S-nitrosoglutathione (RVC-588) and 4-phenyl-3-furoxancarbonitrile (RVC-589) as NO donor and precursor, respectively, were studied in terms of their ability to increase b-wave recovery of electroretinogram (ERG) and ocular blood flow. It was found that RVC-588 increased b-wave amplitude markedly from 28% (control) to 67% (treated) and the blood flow significantly in the retina, choroid, and ciliary body. In the case of RVC-589, the b-wave recovery was significantly increased from 30% (control) to 51% (treated) but was less marked than that of RVC-588. The blood flow in the eye tissues was not significantly increased by RVC-588, but there was a clear tendency to enhance in the retina, choroid and iris. These results indicate that NO can be released effectively from S-nitrosothiols but less significantly from furoxans.

Animals↗
PubMed1997

Facilitation of retinal function recovery by coumarin derivatives.

Ischemic retinopathy is a difficult disease to treat, although numerous drugs have been tried in the clinics. Coumarin was one of those tried as an anti-coagulant with a marginal efficacy. In this study, 15 coumarin derivatives were studied on the b-wave recovery in electroretinogram which is an indicator of the functional recovery of retina after ischemic insult. It was found that when positions 6, 7 and 8 were occupied by various functional groups, the b-wave recovery could be markedly enhanced. On the other hand, single occupation of position 3 with any functional group would cause damaging effects to the anti-ischemic activity. It is concluded that some coumarin derivatives with two or all of these positions at 6, 7 and 8 occupied by certain functional groups could result in useful drugs for the treatment of ischemic retinopathy.

Animals↗
PubMed1997

8-(N,N-diethylamino)-n-octyl-3,4,5-trimethoxybenzoate actions on calcium dynamics in cultured vascular smooth muscle cells.

AIM: To study 8-(N,N-Diethylamino)n-octyl-3,4,5-trimethoxybenzoate (TMB), a potent Ca(2+)-antagonist, actions on cellular calcium dynamics in vascular smooth muscle cell (VSMC) cultures. METHODS: A7r5 VSMC were cultured with Fura-2 measurements of intracellular Ca2+ concentration, [Ca2+]i. RESULTS: TMB reduced [Ca2+]i from control levels and blocked [Ca2+]i increase caused by norepinephrine (NE) and 2,5-di (t-butyl)-1,4-benzohydroquinone (BHQ). [Ca2+]i reduction by TMB was further enhanced by ryanodine. CONCLUSION: TMB is an effective agent for blocking the [Ca2+]i increase caused by NE and BHQ and for enhancing the [Ca2+]i reduction caused by ryanodine.

Animals↗
PubMed1997

Actions of 8-(N,N-diethylamino)-n-octyl-3,4,5-trimethoxybenzoate in vascular smooth muscle cell cultures.

AIM: To study the effects of 8-(N,N-diethylamino)-n-octyl-3,4,5-trimethoxybenzoate (TMB-8) on vascular smooth muscle (VSM) cells A7r5. METHODS: The effects of TMB-8 were investigated in A7r5 cell cultures with 45CaCl2. RESULTS: TMB-8 reduced the intracellular free Ca2+ concentration, [Ca2+]i in a Ca(2+)-free medium and blocked Ca2+ entry from the extracellular site in a regular Ca2+ medium. The equilibrated total cellular binding of Ca2+ was increased by TMB-8 whereas 45Ca2+ entry activated by both NE and KCl was inhibited. However, the NE-activated Ca2+ entry was not blocked by TMB-8 if TMB-8 was added together with 45Ca2+ at a later time instead of by pretreatment. Similar to actions of NE and KCl, depletion of Ca2+ from sarcoplasmic reticulum (SR) would also activate Ca2+ entry, which was blocked by TMB-8. When TMB-8 was rinsed out alone or together with NE after pretreatment with NE plus TMB-8 in VSM cells, the inhibitory effect of TMB-8 was not affected. CONCLUSION: TMB-8 not only blocks Ca2+ entry from the extracellular site, but also enhances Ca2+ uptake into SR which, indirectly inhibits Ca2+ entry from the extracellular site.

Animals↗
PubMed1997

[Effects of microinjection of sodium glutamate and glycine into ventrolateral nucleus of tractus solitarius on the discharges of phrenic nerve in rabbits].

The effects of microinjection of sodium glutamate and glycine into ventrolateral nucleus of tractus solitarius (VLNTS) on the discharges of phrenic nerve were observed on 40 anaesthetized, vagotomized, paralyzed and artificially ventilated rabbits. The results were as follows: Phrenic nerve discharges were increased, inspiratory duration prolonged, expiratory duration shortened and respiratory frequency not changed by microinjection of sodium glutamate into VLNTS. While by microinjection of glycine, phrenic nerve discharges were decreased, even abolished, inspiratory duration shortened, expiratory duration irregularly prolonged and respiratory frequency decreased. The above results show that VLNTS exert important effects on the genesis of respiratory rhythm.

Animals↗
PubMed1996

Polymorphisms at the 5'-end of the apolipoprotein AI gene and severity of coronary artery disease.

Elevated HDL-cholesterol (C) and apo AI are associated with decreased coronary artery disease (CAD) risk. We determined distributions of two MspI polymorphisms of the apo AI gene, associated in other studies with increased HDL-C, among 644 patients aged < or = 65 years in relation to circulating lipids and CAD severity assessed angiographically. The rare allele distributions at both sites were in Hardy-Weinberg equilibrium in these patients but the base changes were not associated with HDL-C and apo AI levels. However, patients homozygous for the -75 bp substitution were more likely to have one or more significantly diseased vessels (> 50% luminal obstruction)(OR: 4.75, 95%CI: 1.10- 20.46) as also were patients with the rare +83 bp alleles (OR: 2.56, 95%CI: 1.13-5.81). While there was an additive effect of the two polymorphisms to have severe CAD (OR: 6.33, 95%CI: 1.33-30.02), the polymorphism at +83 bp remained significant in predicting CAD severity after adjusting for other variables in a logistic regression analysis (OR: 2.95, 95%CI: 1.26-6.90), which was also strongly associated with the positive family CAD history (P = 0.009). We conclude that patients with these base changes in this Australian coronary population do not have increased HDL-C and apo AI levels but do have more severe CAD.

Aged↗
PubMed1996

Fused pyrazine mono-n-oxides as bioreductive drugs. II Cytotoxicity in human cells and oncogenicity in a rodent transformation assay.

PURPOSE: To determine what structural moieties of the fused pyrazine mono-N-oxides are determining factors in their in vitro cytotoxicity and oncogenicity. METHODS AND MATERIALS: A new series of experimental bioreductive drugs, fused pyrazine mono-N-oxides, was evaluated in vitro for aerobic and hypoxic cytotoxicity in the HT29 human colon adenocarcinoma cell line by using clonogenic assays. The relative oncogenicities of these compounds were also determined in aerobic cultures of C3H 10T1/2 mouse embryo fibroblasts by using a standard transformation assay. RESULTS: Removal of the 4-methyl piperazine side chain from the parent compound, RB 90740, reduced the potency of the hypoxic cytotoxin. Reduction of the N-oxide function increased the aerobic cytotoxicity and eliminated most of the hypoxic/aerobic cytotoxic differential. The reduced N-oxide also had significant oncogenicity, consistent with a mechanism of genotoxicity following bioreduction of RB 90740. CONCLUSION: This new series of bioreductive compounds may be effective in cancer therapy, particularly the lead compound RB 90740. The oncogenic potential of these compounds is similar to that for other cancer therapies. Further studies should include evaluation of these compounds in vivo and the development of analogs with reduced oncogenic potential and retention of the hypoxic/aerobic cytotoxicity differential.

Animals↗
PubMed1996

Lipoperoxidative injury to macrophages by oxidatively modified low density lipoprotein may play an important role in foam cell formation.

Both oxidatively and malondialdehyde modified low density lipoprotein (Ox-LDL and MDA-LDL) could be recognized by the scavenger receptor and induce intracellular cholesteryl ester accumulation of macrophage. The cholesteryl ester accumulation caused by MDA-LDL could be largely cleared by high density lipoprotein (HDL3), but that caused by Ox-LDL could not be. Further studies showed that Ox-LDL and MDA-LDL all could decrease the binding capacity of HDL3 and increase intracellular thiobarbituric acid reactive substances (TBARS). When macrophages were first cultured with MDA-LDL and then in medium without LDL, the decreased binding capacity of HDL3 was somewhat recovered and the intracellular TBARS did not increase any more. However, if macrophages were first cultured with Ox-LDL, the binding capacity of H DL3 continued to decrease and intracellular TBARS continued to increase. There was a negative correlation (r = -0.81, P < 0.01) between the decreased binding capacity of HDL3 and the increased intracellular TBARS caused by Ox-LDL. These results imply that lipid peroxidative injury to macrophages caused by Ox-LDL play an important role in foam cell formation.

Animals↗
PubMed1996

Inhibitory effects of interleukin-1 blockers on corneal fibroblast proliferation.

The regulation of would healing is one of the most important fields of research in ophthalmology today. Rabbit corneal fibroblast cultures were used to study the effects of interleukin-1 (IL-1) blockers on the proliferation of fibroblasts which is closely related to the wound healing. It was found that IL-1 blockers, such as CK-17, CK-101A, CK-2 and CK-103A, suppress fibroblast proliferation in a concentration-dependent manner. DNA synthesis was significantly inhibited by CK-17 and CK-103A but not by CK-101A and CK1-102. Although the synthesis of mRNA was reduced by all CK-compounds at most concentration tested, the synthesis of protein was only slightly reduced or unaffected. These results indicate that CK-compounds are potent fibroblast inhibitors but not cytolytic agents.

Acridines↗
PubMed1996

Effects of Chinese herbal products on mammalian retinal functions.

Ocular ischemia and inflammation are two major factors which induce retinal degeneration. Treatment of these diseases has been difficult, though numerous agents have been tried. Natural products could be a good field to venture into because various medicinal plants have been used for centuries to treat circulation stasis, inflammation, visual disturbances, and eyesight failure. Tetramethyl-pyrazine, coumarin, methyl tyramine, rescinnamine, apocynin, and hesperetin are some natural products isolated from Chinese herbs for improving ocular blood flow, particularly in the choroid and retina. For ocular inflammation, at least a dozen natural products are reviewed in this article. Among those, matrine, tetrandrine and osthole draw particular attention, because they are effective mainly as interleukin-1 blockers, but not as arachidonate blockers. As a result, these agents are potent anti-inflammatory agents and are even more potent than the prototype corticosteroid, prednisolone. It is hoped that all aforementioned agents can be used to treat retinopathies resulting from ocular ischemia and/or ocular inflammation. Scoparone, corylifolinin, epigallocatechin-3-0-gallate, esculetin, and lespedezaflavanone A are some natural products which can improve retinal functions measured with electroretinogram's b-wave recovery. Further research should be carried out to relate natural products which can improve ocular blood flow and inflammation to retinal function and vice versa.

Animals↗
PubMed1996

Increase of ocular blood flow by some phytogenic compounds.

The effects of a number of phytogenic compounds on ocular blood flow were measured by the colored microsphere technique in rabbits. Methyltyramine and coumarin increased blood flow in all eye tissues tested. The blood flow of iris, ciliary body-iris root, retina and choroid was increased by methyltyramine for 255%, 322%, 189%, and 189%, respectively, and by coumarin for 375%, 193%, 139% and 299%, respectively, at 120 minutes after drug administration. Rescinnamine, apocynin and hesperetin also increased ocular blood flow in all eye tissues except retina. The blood flow of iris, ciliary body-iris root, and choroid was increased by rescinnamine for 344%, 234%, and 199%, respectively; by apocynin for 355%, 152%, and 414%, respectively; and by hesperetin for 265%, 136%, and 204%, respectively, at 120 minutes after drug instillation. These results indicate that these compounds could be used to treat ischemic eye diseases in the future.

Acetophenones↗
PubMed1996

Oncogenic potential of bifunctional bioreductive drugs.

Potential oncogenicity must be a factor of concern in the design and development of novel bioreductive drugs. In the present studies, the cytotoxicity and oncogenic transforming potential of a series of heterocyclic mono-N-oxides, designed to be used as bioreductive drugs, were examined using the mouse C3H 10T1/2 cell system. Exponential phase cultures of 10T1/2 cells were treated with graded doses of the bioreductive drugs for a 4 h period, either in air or hypoxia, at 37 degrees C. After treatment, cultures were replated for both survival and transformation assays. The fused pyrazine mono-N-oxide RB 90740 and its N-deoxy analogue, RB 92816, demonstrated a dose-dependent cytotoxicity and oncogenic transforming potency under aerobic conditions. Similarly, the indoloquinone E09 and the structurally related mitomycin C demonstrated dose dependence in both toxicity and oncogenic transforming potential. The most cytotoxic aromatic-N-oxides tested, RB 92816, also demonstrated the highest oncogenic transformation incidence. In hypoxia, the bioreductive metabolites of RB 90740 were substantially more cytotoxic and induced a higher oncogenic transformation yield than the drug in air. These data are consistent with the structure-activity relationship for bioreductive drugs in that heterocyclic-N-oxides with reactive side chains such as RB 92816 are cytotoxic and potentially carcinogenic.

Animals↗
PubMed1995

Ocular hypotensive effects of L-arginine and its derivatives and their actions on ocular blood flow.

Effects of L-arginine and some related compounds on the intraocular pressure recovery (IOPR) and ocular blood flow in rabbits had been studied. It was found that L-arginine (RVC-579) and N alpha-benzoyl-L-arginine ethyl ester (RVC-578) delayed the IOPR markedly: The IOPR of the contralateral non-treated eye was delayed to the same extent as the treated eye. The effects of closely related congeners L-(+)-canavanine (RVC-581) and L-homoarginine (RVC-580) on the IOPR were qualitatively similar to RVC-579 and RVC-578 but less effective. RVC-578 was found to increase the blood flow significantly in ciliary body, retina and choroid. On the other hand, NG-nitro-L-arginine, a nitric oxide (NO) synthase inhibitor, reduced the blood flow in choroid at 60 and 120 min after drug administration and did not increase the blood flow in iris, ciliary body and retina. These results indicate that L-arginine and its derivative are capable of lowering the IOP possibly through the formation of nitric oxide to relax the blood vessel and to reduce the IOP as a result.

Animals↗
PubMed1995

Vaninolol: a novel compound for the treatment of glaucoma and ischemic retinopathy.

Vaninolol has been confirmed as a selective beta 1-adrenergic blocking agent. The new compound was studied for its effects on intraocular pressure (IOP), the ocular blood flow and the retinal function in this report. Vaninolol showed marked delay in IOP recovery demonstrating that the agent possessed an ocular hypotensive action. This effect is equipotent or slightly more active than L-timolol. In addition, effects of vaninolol on the ocular blood flow of ocular hypertensive eyes were determined using the colored microspheres technique. It was found that vaninolol improved the ocular blood flow in ciliary body and retina, but not in iris and choroid. Further, vaninolol is able to improve the b-wave recovery in electroretinography significantly, indicating that it is possible to develop a new agent for the treatment of ischemic retinopathy.

Adrenergic beta-Antagonists↗
PubMed1995

Improvement of retinal functions after ischemia with L-arginine and its derivatives.

Retinal ischemia was created by occlusion of rat central retinal artery for 30 minutes. The loss of retinal function was indicated by the loss of b-wave of electroretinogram. The recovery of retinal function after reperfusion of central retinal artery was observed with the gradual recovery of b-wave amplitude to approximately 20% of original b-wave amplitude. When L-arginine (RVC-579) was administered at the time of retina ischemia, the b-wave amplitudes recovered up to 64% of original height and were significantly higher than corresponding controls at 120, 180, and 240 min after ischemia. When the derivative of L-arginine, N alpha-benzoyl-L-arginine ethyl ester (RVC-578), was administered, the b-wave recovery was significantly higher than corresponding controls at 90, 120, 180, and 240 min after ischemia; the recovery reached 51% of the original b-wave value. These results indicate that the L-arginine and its lipophilic derivatives could be used for the treatment of ischemic retinopathy. Since L-arginine is a natural amino acid, it is not expected to produce major side effects, if any, and could pave the way for the development of a safer drug to be used in the clinics. Compounds which increase the formation of NO in vivo, dilate blood vessels. Both L-arginine and RVC-578 can be placed in this category. They may improve effects of retinal ischemia by increasing NO production.

Animals↗