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Biomedical subjects

P Chan

Publications and source records attributed to P Chan.

At least 163 records · Page 9Linked to original sources
PubMed1995

Trilinolein reduces infarct size and suppresses ventricular arrhythmias in rats subjected to coronary ligation.

Trilinolein, a triacylglycerol with linoleic acid as the only fatty acid residue in all esterified positions of glycerol, was previously found to improve erythrocyte deformability in vitro. In this study, the in vivo antiarrhythmic and anti-ischemic effects of trilinolein in coronary ligated rats were investigated. Male Sprague-Dawley rats were anaesthetized with urethane. Trilinolein, at dosages ranging from 10(-11) to 10(-7) g/kg, was administered intravenously 15 min before ligation of coronary artery. Also, the effect of trilinolein on arrhythmia was studied by ligating the coronary artery for 30 min, then reperfusing myocardium for 10 min. During the 30-min ischemia, trilinolein reduced not only the number of ectopic beats but also the incidence rate and duration of ventricular tachycardia. At 10(-7) g/kg, trilinolein completely suppressed all ventricular arrhythmias. Ventricular arrhythmias during 10 min reperfusion were also reduced by trilinolein at similar dosages. Furthermore, the effect of trilinolein on infarct size was evaluated by occluding the coronary artery for 4 h before the infarct zone was stained and weighed. In rats subjected to 4 h coronary ligation, pretreatment with 10(-7) g/kg trilinolein at 15 min prior to the coronary ligation significantly reduced infarct size. Trilinolein may protect myocardium against ischemic injury and suppress arrhythmia during ischemia and reperfusion.

Animals↗
PubMed1995

Acute heroin intoxication with complications of acute pulmonary edema, acute renal failure, rhabdomyolysis and lumbosacral plexitis: a case report.

After intravenous injection of heroin, a 27-year-old male with altered mental status and hypotension was seen at the Emergency Service where acute pulmonary edema was noted. The problem was resolved three days later after oxygen therapy had been administered by face mask. Acute renal failure, rhabdomyolysis and monoplegia of the patient's left leg were exhibited during his stay at the Intensive Care Unit. Neurological examination and electro-diagnostic studies (electromyography and nerve conduction velocity) showed left lumbosacral plexitis. Hemodialysis was given. Though the patient's hospital course was uneventful, satisfactory recovery from his left leg weakness, which persisted for one year after hospital discharge, was finally achieved.

Acute Disease↗
PubMed1995

Successful percutaneous transluminal angioplasty in native coarctation of aorta in young adult: a case report.

Coarctation of aorta is a rare cause of secondary hypertension, premature death will occur if no appropriate treatment is given. Before 1980, the only effective treatment was surgery, and recurrent stenosis was frequent. After then several works on percutaneous transluminal angioplasty of this disease were reported, with promising short-term and long-term results, especially in children and young adults. This report concerns a 19-year-old male who had hypertension for four years; the hypertension was caused by coarctation of the aorta, confirmed by cardiac catheterization and angiography. Average blood pressure (BP) of his upper extremities was 200/110 mmHg which dropped to 150/90 mmHg immediately, and still two years, after angioplasty, whereas BP of the lower extremities maintained at about 150/80 mmHg measured by Korotkoff technique. Follow-up transesophageal echocardiography found no coarctation or aneurysm at the dilatation site one year later. Magnetic resonance imaging, performed two years later, showed an almost normal aortic wall at the coaxctation. The postoperative course was uneventful, and patient follow-up at the cardiology clinic has regularly shown an average BP around 150/80 mmHg.

Adult↗
PubMed1995

Lazaroids and deferoxamine attenuate the intracellular effects of oxyhaemoglobin in vascular smooth muscle.

OBJECTIVES: While it is probable that the cerebrovascular spasm which occurs after subarachnoid haemorrhage results from the action of haemoglobin, the mechanism of that process remains unclear. These studies were thus designed to test the hypothesis that the action of oxyhaemoglobin results from the iron-catalyzed formation of free radicals and subsequent lipid peroxidation resulting in intracellular changes in the second messengers for contraction. METHODS: Levels of intracellular calcium and of inositol (1,4,5)-trisphosphate were measured in cultured vascular smooth muscle cells derived from primate cerebral arteries. Contractility of rings of canine cerebral vessels were examined in vitro using standard pharmacological techniques. Vessels in spasm were obtained from the "two haemorrhage" canine model and the presence of vasospasm was confirmed angiographically. In each case, the effects of oxyhaemoglobin and sometimes of free radicals generated from iron salts were examined in the presence and in the absence of free-radical scavenging agents or the iron chelating agent, deferoxamine. RESULTS: Oxyhaemoglobin produces a slowly-developing sustained contraction of arterial rings which is accompanied by a sustained elevation of intracellular calcium. It also produces a transient but significant elevation of inositol (1,4,5)-trisphosphate, but this is not correlated with the development of sustained constriction. Deferoxamine and the lazaroid compounds U-74389G and U-83836E were effective in preventing the effects of oxyhaemoglobin and free radicals in the models tested, although in vessels in spasm, all effects were smaller. CONCLUSIONS: The present study provides results which are consistent with the hypothesis that the actions of haemoglobin on vascular smooth muscle are mediated by the formation of free radicals which subsequently affect intracellular calcium concentrations. This also implies that agents which impair free radical production or other processes leading to iron-catalyzed lipid peroxidation, are of potential value in cerebrovascular spasm.

Animals↗
PubMed1995

Thrombophilia associated with obesity in ethnic Chinese.

OBJECTIVE: To investigate a possible interrelationship between obesity and the coagulation and fibrinolytic systems of ethnic Chinese. DESIGN: The Cardiovascular Disease Risk Factor Two-Township Study, a longitudinal, prospective study in Taiwan, which focuses on the evolution of cardiovascular disease risk factors. MEASUREMENTS: Haemostatic parameters measured in this study included prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, factor VIIc, factor VIIIc, antithrombin III and plasminogen. RESULTS: Present data demonstrated that all haemostatic parameters show a dose-dependent change with body weight. PT and APTT shortened with increased body mass index (BMI). Fibrinogen, factor VIIc, factor VIIIc, plasminogen and antithrombin III increased with higher BMI. CONCLUSION: The present result shows that haemorrheological abnormalities do exist in obese subjects and this thrombophilic phenomenon sheds further light on the study of higher cardiovascular and cerebrovascular mortality and morbidity in the obese.

Adult↗
PubMed1994

Comparative mapping of lipocalin genes in human and mouse: the four genes for complement C8 gamma chain, prostaglandin-D-synthase, oncogene-24p3, and progestagen-associated endometrial protein map to HSA9 and MMU2.

The lipocalin superfamily encompasses a large set of quite distantly related proteins that act as carriers for small, lipophilic molecules. The lipocalin genes coding for orosomucoid, the alpha 1-microglobulin/bikunin precursor, and the major urinary protein map to MMU4, while their human counterparts map to the homologous HSA9q34 area where three other lipocalin genes for complement C8 gamma chain (C8G), progestagen-associated endometrial protein (PAEP), and prostaglandin D synthase (PTGDS) are also located. By linkage analyses in an interspecific backcross progeny in mouse, the Lcn2 gene coding for the oncogenic lipocalin 24p3, as well as the 3 lipocalin genes for C8G, PTGDS, and PAEP, have now been assigned to MMU2. The first three genes map to proximal MMU2, which is known to be homologous to HSA9q34. Paep is more distally located, which extends the number of regions with conserved syntenies between HSA9q34 and MMU2. By in situ hybridization, the human LCN2 gene maps to HSA9q34. Our data indicate that the lipocalin locus arrangement in the human/mouse ancestor is closer to that found at HSA9q than to that in the MMU genome.

Acute-Phase Proteins↗
PubMed1994

Leukemia induced in rats but not mice by dimethyl morpholinophosphoramidate, a simulant anticholinesterase agent.

Dimethyl morpholinophosphoramidate (DMMPA), an organophosphate, caused leukemia in male and female Fischer 344/N rats. DMMPA was administered in corn oil by oral intubation to groups of 50 male and 50 female rats at 0, 150, 300, or 600 mg/kg body weight, five times per week for 2 years. B6C3F1 mice were given 0, 150 (males only), 300, and 600 (females only) mg/kg body weight under the same schedule. DMMPA induced a dose-related enhancement in the incidence of mononuclear cell leukemia in rats--males: controls = 14/50, 150 mg group = 21/50; 300 mg group = 19/50; 600 mg group = 25/50; females: controls = 9/50, 150 mg group = 13/50; 300 mg group = 12/49; 600 mg group = 18/50. Survival-adjusted rates strengthen the DMMPA effect: males--31%, 50%, 47%, and 63%; females--20%, 32%, 30%, 50%. Latent periods for mononuclear cell leukemia development in exposed rats were not shortened compared to controls. No carcinogenic effects in mice were detected. DMMPA was not mutagenic in Salmonella, was mutagenic for mouse lymphoma cells, and induced both chromosome aberrations and sister chromatid exchanges in Chinese hamster ovary cells.

Administration, Oral↗
PubMed1994

Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on levels of glutamate and aspartate in the mouse brain.

Perturbations of energy metabolism and activation of N-methyl-D-aspartate (NMDA) receptors have been suggested to play a role in the neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In the present study, the concentrations of the excitatory amino acids, L-glutamate and L-aspartate, were evaluated in the mouse brain after administration of MPTP and correlated with MPTP-induced energy impairment. Levels of glutamate and aspartate were determined in the brain of C57BL/6 mice exposed to a single dose of MPTP (40 mg/kg, s.c.). MPTP significantly decreased glutamate and aspartate concentrations in the striatum and ventral mesencephalon but not in the cerebellar cortex 4 h after MPTP administration. This effect was only temporary, however, since glutamate and aspartate concentrations returned to control levels 24 h after MPTP exposure. Pretreatment with the monoamine oxidase B inhibitor deprenyl (10 mg/kg, i.p.) or the catecholamine uptake blocker mazindol (20 mg/kg, s.c.) 30 min before MPTP administration prevented MPTP-induced decrease in glutamate and aspartate. Moreover, injection of 2-deoxyglucose, a competitive inhibitor of cellular glucose transport and utilization, significantly potentiated MPTP-induced decrease in striatal levels of glutamate and aspartate. The present results indicate that systemic administration of MPTP causes a decrease in tissue concentrations of glutamate and aspartate in the striatum and ventral mesencephalon. These effects may result from the perturbation of energy metabolism induced by MPTP in the nigrostriatal dopamine system.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1994

Cardiovascular effects of R-alpha-methylhistamine, a selective histamine H3 receptor agonist, in rats: lack of involvement of histamine H3 receptors.

Selective histamine H3 receptor agonists, such as R-alpha-methylhistamine, have been shown to inhibit neurogenic sympathetic pressor responses in vivo. The objective of the present study was to test the hypothesis that R-alpha-methylhistamine would evoke an histamine H3 receptor mediated hypotensive response in an animal with intact sympathetic vascular tone. In pentobarbital anaesthetized rats, administration of R-alpha-methylhistamine (0.1-3 mg.kg-1, i.v.) had a biphasic effect on arterial pressure, consisting of a transient depressor response followed by a more long-lasting pressor response. The depressor response was antagonized by chlorpheniramine (selective histamine H1 receptor antagonist, 3 mg.kg-1, i.v.), but was unaffected by cimetidine (selective histamine H2 receptor antagonist, 3 mg.kg-1, i.v.) or thioperamide (selective histamine H3 receptor antagonist, 3 mg.kg-1, i.v.). The pressor response was unaltered by chlorpheniramine, cimetidine or thioperamide. In pithed rats, R-alpha-methylhistamine had a biphasic effect on arterial pressure which was qualitatively similar to that seen in anaesthetized rats with the exception that the pressor responses were much greater in magnitude and duration and were accompanied by significant increases in heart rate. On a pharmacological basis, the biphasic response in pithed rats was identical to that seen in anaesthetized rats inasmuch as the depressor response was antagonized by chlorpheniramine whereas the pressor response was resistant to histamine H1, H2 and H3 receptor antagonists. Combined alpha- and beta-adrenoceptor blockade (with phentolamine and nadolol) produced significant attenuation of the pressor and tachycardic responses to R-alpha-methylhistamine in pithed rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗
PubMed1994

Consistent responses of the human vascular smooth muscle cell in culture: implications for restenosis.

PURPOSE: The mechanisms whereby restenoses occur at discrete sites within the vasculature remain uncertain. We have recently reported that vascular smooth muscle cells (VSMC) derived from patients with graft stenoses are resistant to growth inhibition by heparin. In this study, we have examined whether VSMC proliferation rates and responses to inhibition by heparin vary according to the individual or the anatomic site of origin. METHODS: Long saphenous veins from seven patients were divided into proximal, middle, and distal portions, and VSMC were cultured separately from each. VSMC proliferation in response to 15% fetal calf serum +/- 100 micrograms/ml heparin was measured by counting triplicate samples at 0, 3, 7, 10, and 14 days. This experiment was repeated from the second to the sixth passage (n = 6) and for artery and vein pairs derived from four additional patients. RESULTS: Differences between vein segment cultures of individual veins were found not to differ significantly from experimental error for either proliferation or heparin inhibition and were not altered by repeated passage (ANOVA). There were, however, significant differences in sensitivity to heparin inhibition between patients (p = 0.02) (ANOVA). There were no significant differences between paired samples of artery and vein for either proliferation or heparin inhibition (Mann-Whitney test). CONCLUSIONS: VSMC growth characteristics reflect the individual patient and are maintained in cell culture.

Analysis of Variance↗
PubMed1994

Venous reflux in patients with previous deep venous thrombosis: correlation with ulceration and other symptoms.

PURPOSE: Deep vein thrombosis (DVT) in many cases leads to chronic symptoms in the damaged leg, even though the affected veins have recanalized. The major hemodynamic defect in such recanalized veins is reflux. The incidence and extent of reflux has been studied in patients with proven DVT and correlated with concurrent symptoms. METHODS: Two hundred seventeen limbs in 183 patients were examined by duplex scanning from January 1989 to October 1992. All limbs had previous DVT diagnosed by venography. Sites and extent (proximal, distal, or both) of reflux were identified by meticulous duplex scanning of the whole venous system and correlated with presenting symptoms. RESULTS: The patients were classified into nine groups on the basis of the classification of the system involved (superficial, deep, or superficial and deep) and whether the reflux was found proximal or distal to the knee or both. Eight-one limbs belong to chronic venous insufficiency class 1, 92 belong to class 2, and 38 belong to class 3. Reflux was confined to the deep venous system in 84 limbs (38.7%), to the superficial system in 31 (14.3%) limbs, and to both systems in 102 (47%) limbs. It was confined to proximal veins only in 48 (22.1%) limbs, distal only in 56 (25.8%) limbs and throughout the limb in 113 (52.1%) limbs. The incidence of swelling was increased by distal or a combination of proximal and distal reflux regardless of which system was involved. In limbs with superficial venous insufficiency (SVI) or deep venous insufficiency (DVI) only, the incidence of skin changes was not affected by the extent of reflux. However, in limbs with combined SVI and DVI, it was increased in the presence of reflux throughout the limb. Absence of distal reflux was associated with a low incidence of skin changes even in the presence of DVI. Ulceration increased with an increased extent of reflux in the presence of SVI. Absence of superficial reflux was associated with a low incidence, even in the presence of DVI. CONCLUSIONS: The data suggest that as far as the skin changes and ulceration are concerned, distal reflux and reflux in the superficial veins are more harmful than reflux confined to the deep veins, even when such reflux extends throughout the deep venous system.

Adolescent↗
PubMed1994

Superficial venous insufficiency: correlation of anatomic extent of reflux with clinical symptoms and signs.

PURPOSE: The aim of this study was to assess the distribution and extent of valvular incompetence in patients with reflux confined to the superficial venous system and correlate the extent of such reflux with clinical symptoms and signs. METHODS: Two hundred fifty-five limbs of 217 patients with superficial venous insufficiency and normal perforating and deep veins were examined with color-flow duplex imaging. One hundred twenty-three limbs (48.2%) of 102 patients had reflux confined to the long saphenous system, 83 limbs (32.6%) of 72 patients had reflux confined to the the short saphenous system, and 49 limbs (19.2%) of 43 patients had reflux in both long and short saphenous systems. RESULTS: In the long saphenous system the commonest pattern of reflux was that which extended throughout the length of long saphenous vein (LSV) (47%). Ache, swelling, and skin changes were common in the presence of below knee reflux irrespective whether the thigh segment was involved. Ulceration (8%) was found only in limbs with reflux extending throughout the length of LSV. In the short saphenous system the most common pattern of reflux extended throughout the length of short saphenous vein (SSV) (57%) without involvement of Giacomini or gastrocnemial veins. Ache and swelling were present in 62% and 72% of the limbs, but this incidence was not related to the extent of reflux. Swelling, skin changes, and ulceration occurred only when the whole of the SSV was involved. In the limbs with reflux in both the long and short saphenous systems, the most common pattern of reflux extended throughout the length of both systems (45%). In these limbs the incidence of swelling was 80%. The incidence of skin changes went from 44% when the below-knee segment of the LSV was involved to 73% when reflux occurred throughout the LSV and SSV. Ulceration (14%) was found only in the latter situation. Variable patterns of saphenogastrocnemial termination were seen. In 57.8% of the limbs SSV joined the popliteal vein just above the popliteal crease, whereas the SSV terminated in the thigh in 26.6%. CONCLUSIONS: We conclude that ache, ankle edema, and skin changes in limbs with reflux confined to the superficial venous system are predominantly associated with reflux in the below-knee veins. Ulceration is found only when the whole of the LSV is involved (8%) or when reflux is extensive in both LSV and SSV (14%).

Adolescent↗
PubMed1994

Rapid ATP loss caused by methamphetamine in the mouse striatum: relationship between energy impairment and dopaminergic neurotoxicity.

To study the relationship between energy impairment and the effects of d-methamphetamine (METH) on dopaminergic neurons, ATP and dopamine levels were measured in the brain of C57BL/6 mice treated with either a single or four injections of METH (10 mg/kg, i.p.) at 2-h intervals. Neither striatal ATP nor dopamine concentrations changed after a single injection of METH, but both were significantly decreased 1.5 h after the multiple-dose regimen. The effects of METH on ATP levels appear to be selective for the striatum, as ATP concentrations were not affected in the cerebellar cortex and hippocampus after either a single or multiple injections of METH. In a second set of experiments, an intraperitoneal injection of 2-deoxyglucose (2-DG; 1 g/kg), an inhibitor of glucose uptake and utilization, was given 30 min before the third and fourth injections of METH. 2-DG significantly potentiated METH-induced striatal ATP loss at 1.5 h and dopamine depletions at 1.5 h and 1 week. These results indicate that a toxic regimen of METH selectively causes striatal energy impairment and raise the possibility that perturbations of energy metabolism play a role in METH-induced dopaminergic neurotoxicity.

Adenosine Triphosphate↗
PubMed1994

Growth inhibition of human vascular smooth muscle cells by fenofibrate: a possible therapy for restenosis.

OBJECTIVE: The aim was to assess the growth inhibitory effect of fibrates on human vascular smooth muscle cells. Restenosis is the most important factor limiting the long term success of invasive vascular interventions and there is as yet no effective preventive treatment. Platelet derived growth factor (PDGF) is considered to be an important growth promoting agent for vascular smooth muscle cells (VSMC) and fenofibric acid (a hypolipidaemic drug) has been reported to be a PDGF antagonist. METHODS: The effect of the fibrate drugs fenofibrate, clofibrate, bezafibrate, and gemfibrozil were examined on the proliferation of cultured human vascular smooth muscle cells derived from saphenous vein (n = 20) and graft stenoses (n = 7). RESULTS: Fenofibrate (100 microM) produced potent inhibition (48%) of VSMC proliferation at a concentration equivalent to that of its circulating metabolite fenofibric acid, but none of the other drugs produced any significant effect on growth. VSMC derived from graft stenoses were equally sensitive to inhibition as saphenous vein derived controls, in contrast to our previous work which reported that graft stenosis derived VSMC were resistant to growth inhibition by the physiological inhibitor heparin. The antiproliferative effect of fenofibrate was independent of inhibition of cellular cholesterol synthesis or toxicity. Fenofibrate inhibited VSMC growth induced by 15% fetal calf serum, PDGF, and basic fibroblast growth factor to a similar degree, indicating that it is not a specific PDGF antagonist. CONCLUSIONS: Fenofibrate is not a specific PDGF antagonist. Fenofibric acid, one of the principal metabolites of fenofibrate, did not produce any inhibition of growth, suggesting that oral administration of fenofibrate would not be efficacious. Fenofibrate is the first potent inhibitor to be described for VSMC derived from human myo-intimal hyperplastic lesions.

Bezafibrate↗
PubMed1994

Effect of calcium channel blockers on the growth of human vascular smooth muscle cells derived from saphenous vein and vascular graft stenoses.

Vascular restenosis after invasive interventions is an important clinical problem for which no preventive pharmacologic therapy exists. Calcium channel blockers have been shown to inhibit myointimal hyperplasia in animal models of restenosis and in some small and flawed clinical coronary restenosis trials. We examined the inhibitory effect of amlodipine, verapamil, and diltiazem on the growth of cultured human vascular smooth muscle cells (VSMC) derived from saphenous vein (n = 20) and graft stenoses (n = 7), in 14-day proliferation assays and [methyl 3H]thymidine uptake studies. Amlodipine and verapamil produced significant inhibition (30%) of VSMC proliferation and DNA synthesis at 10 microM but not at 500 nM-1 microM. To our knowledge, this is the first study to examine the antiproliferative effect of calcium channel blockers in VSMC derived from human graft stenoses. Growth inhibition of VSMC from graft stenoses was not significantly different from that of control saphenous vein-derived cells. We conclude, therefore, that calcium channel blockers inhibit human VSMC proliferation in vitro, regardless of whether the cells were grown from graft stenoses or saphenous vein. However, the concentrations at which these calcium channel blockers elicit antiproliferative effects may not be attainable during therapeutic dosing in humans.

Amlodipine↗
PubMed1994

Trilinolein improves erythrocyte deformability during cardiopulmonary bypass.

The in vitro effect of trilinolein, a triglyceride with linoleic acid as the major fatty acid residue in the esterified positions of glycerol, on erythrocyte deformability was studied in blood samples collected from 12 patients before and after cardiopulmonary bypass (CPB). Erythrocyte deformability was measured with a filtration method and expressed as red cell filtration rate (RFR). RFR was reduced after CPB and the reduction was time dependent. Trilinolein at a concentration of 10(-7) M significantly reversed the CPB-induced reduction of RFR when it was mixed with blood samples collected 30, 60 and 90 min from the start of CPB. This study confirmed the effect of CPB on erythrocyte deformability and showed that this damage could be significantly improved by mixing blood with trilinolein.

Cardiopulmonary Bypass↗
PubMed1994

Inhibition of human vascular smooth muscle cell proliferation by lovastatin: the role of isoprenoid intermediates of cholesterol synthesis.

Restenosis remains the largest single obstacle to the long-term success of invasive vascular interventions. Lovastatin, an HMG-CoA reductase inhibitor, has been shown to reduce myointimal hyperplasia in animal models of restenosis and in one clinical coronary restenosis trial. We have assessed the effect of lovastatin on the growth of cultured human vascular smooth muscle cells derived from saphenous vein and vascular graft stenoses. Lovastatin (2 microM) inhibited proliferation over 14 days in saphenous vein (and graft stenoses) derived vascular smooth muscle cells by 42% and 32% respectively: this was not significantly different. Lovastatin (10 microM) reduced [methyl 3H]-thymidine uptake by 51% in saphenous vein-derived cells. These concentrations were significantly higher than those achieved in plasma during therapeutic dosage. Lovastatin-induced inhibition of vascular smooth muscle cell proliferation and [methyl 3H]-thymidine uptake was completely reversed by adding mevalonate (100 microM) but cholesterol (10-40 micrograms ml-1) had no effect. Isopentenyl adenine (25-50 microM) did not affect the inhibition of [methyl 3H]-thymidine uptake by lovastatin (10 microM), but farnesol (20 microM), another isoprenoid precursor of cholesterol synthesis, reversed the antiproliferative effect.

Adenine↗