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Biomedical subjects

S W Chang

Publications and source records attributed to S W Chang.

At least 55 records · Page 3Linked to original sources
PubMed1995

Early change of vascular permeability in hypercholesterolemic rabbits.

To study the effect of hyperlipidemia on vascular permeability, serial anterior chamber fluorophotometric examinations were carried out on 33 control rabbits (group 1) and 32 diet-induced hypercholesterolemic (group 2) rabbits. Changes in the blood-aqueous barrier function associated with total serum cholesterol (CHO) and triglyceride (TG) levels were studied at the beginning of the study and every 2 weeks thereafter for up to 16 weeks following 0.5% cholesterol-enriched diet feeding. Concurrently, a slit-lamp biomicroscope was used to examine the iris for evidence of atheromatous plaque. In group 1, the CHO level decreased slightly during the first 6 weeks and remained rather steady thereafter. The status of the blood-aqueous barrier correlated significantly with serum CHO and TG levels (r = .46, P < .001; r = .23, P = .01, respectively). In group 2, CHO and TG levels increased significantly after 2 and 8 weeks of cholesterol-enriched diet feeding, respectively. The blood-aqueous barrier also became more permeable than that in group 1 after 2 weeks' and increased above its baseline level after 6 weeks' feeding. Both CHO and TG levels correlated well with the degree of blood-aqueous barrier breakdown (r = .51, P < .001; r = .25, P < .001, respectively). The first evidence of iridic lipid-streak deposition was noted at 7.6 +/- 0.7 weeks, while definite iridic atheromatous plaque appeared 11.2 +/- 0.7 weeks after feeding. The change in the blood-aqueous barrier also correlated well with the semiquantitative score of iridic plaque (r = .58, P < .001) and usually preceded visual evidence of plaque formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Clinical evaluation of ciprofloxacin ophthalmic solution in the treatment of refractory bacterial keratitis.

Ciprofloxacin is a fluoroquinolone antimicrobial agent inhibiting bacterial DNA gyrase, with good in vitro and in vivo activity against many Gram-positive and Gram-negative ocular pathogens. It has low toxicity, low resistance rate and low minimum inhibitory concentration. The purpose of this study was to evaluate the efficacy of ciprofloxacin in treating bacterial keratitis refractory to conventional therapy. Thirty patients with smear-proven bacterial ulcers were treated by conventional therapy. Of these, cultures were positive in 28 (93.3%) patients. Pseudomonas aeruginosa was isolated in 13 (46.4%) patients, nontuberculous mycobacteria in nine (32.1%) and other bacteria in six (21.4%). Fifteen patients (50%) were cured with conventional therapy. Four patients (13.3%) underwent surgery due to impending corneal perforation. Eleven patients were shifted to ciprofloxacin therapy because of poor results with conventional treatment. Of these, eight (72.7%) patients were treated successfully. No adverse events were encountered except a white crystalline precipitate in two cases which resolved spontaneously after discontinuation of therapy. In view of its effectiveness and low toxicity, ciprofloxacin should be considered in treating bacterial keratitis which is refractory to conventional therapy.

Adolescent↗
PubMed1994

Clinicopathologic study of Gore-Tex patch graft in corneoscleral surgery.

Three patients with corneal or scleral defects were treated with Gore-Tex grafting, including one case of corneal ulcer, one case of Mooren's ulcer, and one case of necrotizing scleritis. These eyes remained inflamed after Gore-Tex grafting. The interval between grafting and removal ranged from 2 months to 1 year. Pathologically, none of these grafts showed evident epithelial or fibrous tissue ingrowth of the Gore-Tex graft. Fungal inhabitation was noted in one graft, and fungal endophthalmitis developed 5 months after graft removal and penetrating keratoplasty. Although Gore-Tex offers some advantages, it has disadvantages when it is used without adequate conjunctival covering, including poor epithelialization, poor adhesion between graft and surrounding tissue, and potential infectious route.

Adult↗
PubMed1994

Evans blue dye in the assessment of permeability-surface area product in perfused rat lungs.

Evans blue dye (EBD) has been used extensively as a marker of extravascular protein leakage. We assessed the utility of EBD as an albumin marker in the measurement of permeability-surface area product (PS) in perfused rat lungs and compared the results with PS values obtained using 125I-labeled albumin. In isolated perfused rat lungs, PS was measured by exposure to a perfusate containing EBD (600 micrograms/ml) and 125I-albumin (I microCi) for exactly 3 min, followed by washout of the intravascular space with fresh perfusate for 6 min. In lungs from normal rats, we found that PS obtained by EBD (PS-EBD) was fivefold higher than PS obtained by 125I-albumin (PS-125I) [1.92 +/- 0.32 (SE) vs. 0.42 +/- 0.03 x 10(-2) cm3.min-1.g-1, P < 0.05]. Similarly, in rats pretreated with Salmonella enteritidis lipopolysaccharide (2 mg/kg iv), PS-EBD was much higher than PS-125I (2.01 +/- 0.30 vs. 0.59 +/- 0.08 x 10(-2) cm3.min-1.g-1, P < 0.01). This discrepancy between PS-EBD and PS-125I was not explained by differences in the amount of free marker in perfusate, because the albumin-binding rate for both markers was very high. In addition, prolonged perfusion (40 min) with EBD did not significantly affect pulmonary vasoreactivity or water content in rat lungs. A detailed comparison of the kinetics of lung tissue uptake of EBD followed by parallel uptake of both markers up to 60 min of perfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

TNF potentiates PAF-induced pulmonary vasoconstriction in the rat: role of neutrophils and thromboxane A2.

Both tumor necrosis factor (TNF) and platelet-activating factor (PAF) are released during sepsis and are important mediators of septic lung injury. I investigated the interactions of TNF and PAF on vasoactive responses in the pulmonary circulation. In isolated rat lungs perfused with a cell- and plasma-free physiological salt solution, PAF (0.01- and 0.1-micrograms boluses) caused transient dose-dependent pulmonary arterial and venous constrictions. In vivo pretreatment of the rats with TNF (0.02 or 0.2 mg/kg i.v.) 1 h before lung isolation increased lung myeloperoxidase activity and markedly enhanced PAF-induced pulmonary vasoconstriction without affecting the pressor responses to angiotensin II or hypoxia. In contrast, pretreatment with lipopolysaccharide (10 mg/kg), which increased lung myeloperoxidase to the same extent as TNF, caused only a modest enhancement of PAF-induced vasoconstriction associated with reduced pressor responses to angiotensin II and hypoxia. Ex vivo perfusion of isolated lungs with TNF for 1 h did not affect PAF vasoconstriction. The TNF-induced potentiation of PAF vasoconstriction was not altered by depletion of circulating neutrophils with vinblastine but was blocked by Dazmegrel, a thromboxane synthase inhibitor. Thus, TNF potentiates PAF-induced pulmonary vasoconstriction by an in vivo mechanism that is neutrophil independent but thromboxane dependent. This TNF-PAF interaction likely contributes to the development of pulmonary hypertension during sepsis.

Animals↗
PubMed1994

The epithelial barrier function in clear corneal grafts.

We conducted a corneal epithelial permeability study using a fluorophotometer on 93 eyes of 79 patients with clear corneal grafts. There were 45 males and 34 females, aged 61.6 +/- 10.2 years. All eyes received penetrating keratoplasty at least 1 year (mean 40.4 +/- 31.3 months) before examination. The normal fellow eyes of 65 subjects were examined as controls. The averaged corneal epithelial permeability of grafted corneas was significantly higher than that of controls (p < 0.001). In the 65 individuals having an otherwise healthy fellow eye, the grafted corneas were significantly more permeable than their control fellow eyes verified by paired t test (n = 65, p = 0.006). Concomitant corneal sensitivity test revealed a significantly hypesthetic cornea. These results show that in spite of a clinically normal clear graft, there is usually a subnormal epithelial barrier function and reinnervation, even years after corneal transplantation.

Adult↗
PubMed1994

Platelet-activating factor potentiates protamine-induced lung edema. Role of eicosanoids.

Platelet-activating factor (PAF) is a cell membrane-derived ether lipid that plays an important role in acute lung vascular injury. We recently reported that PAF potentiates protamine-induced lung edema by enhancing pulmonary venoconstriction. As PAF is known to stimulate lung eicosanoid synthesis, we investigated the role of peptidoleukotrienes and other eicosanoids in this priming effect of PAF. Addition of PAF (1.6 nM), followed 10 min later by protamine (50 micrograms/ml), to perfusate of salt solution-perfused rat lungs resulted in marked arterial and venous constrictions and severe lung edema. Lung tissue thromboxane B2, 6-ketoprostaglandin F1 alpha and leukotriene C4 (LTC4) were markedly elevated 20 min after PAF/protamine. Pretreatment of the lungs with AA-861, a specific 5-lipoxygenase inhibitor, blocked PAF/protamine-induced leukotriene synthesis, arterial and venous constrictions, and lung edema. In addition, injection of LTC4 (1 microgram) markedly potentiated protamine-induced arterial and venous constrictions and caused lung edema similar to PAF/protamine. Indomethacin, a specific cyclooxygenase inhibitor, also reduced the vasoconstrictive and edemagenic responses to PAF/protamine. However, the pulmonary edema after LTC4/protamine was not blocked by indomethacin. In separate experiments, infusion of this "priming" dose of PAF into isolated perfused lungs induced LTC4 synthesis and augmented lung thromboxane A2 synthesis after arachidonic acid infusion. We conclude that both cyclooxygenase and lipoxygenase products of arachidonic acid metabolism are involved in PAF-induced potentiation of protamine lung edema.

Animals↗
PubMed1994

Chronic biliary obstruction induces pulmonary intravascular phagocytosis and endotoxin sensitivity in rats.

Endotoxin sensitivity varies among animal species and appears to correlate with the presence of pulmonary intravascular macrophage (PIM). In rats, which lack PIM, we investigated the hypothesis that chronic cholestatic liver injury leads to induction of PIM and endotoxin sensitivity. Rats were randomized to either common bile duct ligation (BDL) or sham-surgery and studied at 1 wk (acute cholestasis), 2 wk (cholestasis, early cirrhosis), and 4 wk (cholestasis, established cirrhosis) after surgery. Intravascularly injected fluorescent latex microspheres (1 micron diameter) were taken up by large phagocytic cells in lung parenchyma of BDL rats (at 2 and 4 wk), while no uptake was observed in lungs from control rats. Electronmicroscopy revealed accumulation of large, mononuclear, macrophage-like cells containing ingested latex particles within the pulmonary capillaries. Pulmonary intravascular phagocytosis, as reflected in lung uptake of 99mTc microaggregated albumin (Microlite, mean particle diameter = 1 micron), averaged 0.7 +/- 0.1% (mean +/- SEM) of total injected dose in 13 control rats and progressively increased with time after BDL (1 wk, 1.7 +/- 0.2%; 2 wk, 10.0 +/- 3.0%; 4 wk 35.1 +/- 5.9%). Rats with biliary cirrhosis were markedly sensitive to the lethal effects of low dose endotoxin and demonstrated marked lung edema at the time of death. Furthermore, the lung uptake of intravascular 125I-lipopolysaccharide was increased five-fold in cirrhotic rats. We conclude that chronic biliary obstruction leads to the induction of pulmonary intravascular phagocytes and enhances endotoxin sensitivity in rats. Pulmonary intravascular phagocytosis in patients with advanced cirrhosis may account for their increased susceptibility to sepsis-induced adult respiratory distress syndrome.

Animals↗
PubMed1994

Endotoxin-induced pulmonary leukostasis in the rat: role of platelet-activating factor and tumor necrosis factor.

Injection of bacterial lipopolysaccharide (LPS) into experimental animals induces septic shock associated with the release of tumor necrosis factor (TNF) and platelet-activating factor (PAF). Because both TNF and PAF stimulate neutrophil adhesion to endothelial cells in vitro, and because neutrophils are important effector cells in sepsis-induced lung vascular injury, the role of TNF and PAF in LPS-induced lung neutrophil sequestration was investigated. Lung myeloperoxidase (MPO) activity was measured as a quantitative assessment of pulmonary leukostasis. Injection of Salmonella enteritidis LPS into rats caused dose-dependent increases in lung MPO that peaked at 2 hours and persisted for up to 24 hours. Injection of purified human recombinant TNF (2 to 200 micrograms/kg i.v.) mimicked the effect of LPS on lung MPO activity. Injection of synthetic PAF increased lung MPO only at the highest and lethal dose (10 micrograms/kg). Lower doses (0.1 and 1 microgram/kg) of PAF had no effect on lung MPO by itself and did not enhance LPS- or TNF-induced lung neutrophil sequestration. Furthermore, pretreatment of the rats with two different PAF receptor-antagonists, WEB 2086 (10 mg/kg IP) and SRI 63-441 (10 mg/kg IP), failed to block LPS-induced (1 mg/kg) increase in lung MPO. These data suggest that TNF, not PAF, mediates LPS-induced pulmonary neutrophil sequestration in the intact rat.

Animals↗
PubMed1993

Changes in corneal autofluorescence and corneal epithelial barrier function with aging.

Corneal epithelial permeability studies using fluorophotometers were performed on 90 eyes of 51 normal subjects. After recording the autofluorescence of the cornea (AFC) and of the lens (AFL), we applied 20 microliters of 2% sodium fluorescein to the conjunctival sac. The corneal fluorescence 45 min later (F45), which paralleled the corneal epithelial permeability to fluorescein, was measured by fluorophotometer and analyzed. All parameters of the two eyes of each subject correlated well with each other. There was positive correlation between AFL and patient age and between AFC and patient age (r = 0.78, p < 0.001, and r = 0.74, p < 0.001, respectively). The F45 increased exponentially with advancing age (r = 0.67, p < 0.001). The strong correlation between AFC and AFL in each eye (r = 0.79, p < 0.001) indicated corresponding aging processes in both the cornea and the lens. The increase in epithelial permeability with age possibly represents a subclinical breakdown of barrier function, rendering the corneas more vulnerable to insults.

Adult↗
PubMed1993

Increased pulmonary vascular permeability in rats with biliary cirrhosis: role of thromboxane A2.

Rats with liver cirrhosis exhibit arterial hypoxemia and loss of hypoxic pulmonary vasoconstriction similar to some patients with end-stage liver disease. We hypothesized that the pulmonary circulatory dysfunction in cirrhosis results from vascular endothelial cell injury and interstitial lung edema. To investigate this hypothesis, we compared the extravascular lung albumin leak, lung ultrastructural changes, and tissue eicosanoid levels in control and cirrhotic rats. In comparison to sham-operated controls, rats with biliary cirrhosis, 6 wk after ligation of the common bile duct, had increased lung albumin leak index (1.46 +/- 0.12 vs. 0.80 +/- 0.04, P < 0.001) and bloodless lung wet-to-dry weight ratio (4.94 +/- 0.05 vs. 4.78 +/- 0.03, P < 0.05). Electron-microscopic sections of lungs from cirrhotic rats demonstrated infiltration with intravascular macrophage-like cells, endothelial cell injury, and interstitial edema. In addition, lung tissue thromboxane B2 was significantly increased in cirrhotic rats, and pretreatment with a thromboxane synthase inhibitor, dazoxiben, reduced lung thromboxane B2 level and attenuated extravascular lung albumin leak (control 1.03 +/- 0.07, cirrhotic 2.29 +/- 0.06, cirrhotic plus dazoxiben, 1.57 +/- 0.17). In contrast, WEB 2086, a platelet-activating factor antagonist, had no effect on lung albumin leak. We conclude that pulmonary vascular permeability is increased in rats with biliary cirrhosis and that thromboxane A2 contributes to the pulmonary circulatory abnormalities in cirrhosis.

Albumins↗
PubMed1993

Endotoxin priming followed by high altitude causes pulmonary edema in rats.

Rapid ascent to high altitude may be associated with the development of high-altitude pulmonary edema (HAPE) in susceptible individuals. Because lung lavage fluid obtained from such patients can be rich in protein and neutrophils, we considered that an element of lung injury and inflammation contributed to the pathogenesis of some forms of HAPE. On the basis of such a likely contribution of inflammatory mechanisms, we induced pulmonary lung injury and inflammation by priming rats with Salmonella enteritidis endotoxin (ETX) (0.1 or 0.5 mg/kg body wt ip) and examined the influence of added exposure to simulated hypobaric hypoxia (24 h, 4,300 m). The animals that were primed with ETX and exposed to hypoxia, but not those that received either ETX or hypoxia alone, developed lung vascular damage. This vascular damage manifested itself histologically and by increases in the lung vascular permeability-surface area product and the lung bloodless wet weight-to-dry weight ratio. The bronchoalveolar lavage fluid of ETX-primed hypoxia-exposed rats contained a greater number of white blood cells and a higher concentration of protein compared with that of the ETX-primed rats. Hearts of ETX + hypoxia-treated rats showed an increased ratio of right ventricular weight divided by body weight (RV/BW). Neutropenia prevented the development of pulmonary edema and the increase in ETX + hypoxia rats with a Ca2+ entry blocker inhibited lung injury and RV hypertrophy, these results indicate that ETX priming causes pulmonary edema at high altitude and suggest a role for neutrophils and Ca2+ in this rat model of lung injury.

Altitude↗
PubMed1993

Tissue eicosanoids and vascular permeability in rats with chronic biliary obstruction.

Advanced cirrhosis is known to be associated with extrahepatic organ dysfunction, but the mechanism for this cirrhosis complication is largely unknown. We measured tissue albumin leakage in rats with biliary cirrhosis or acute cholestasis and tested the hypothesis that arachidonic acid metabolites contribute to the vascular permeability change. Six weeks after bile duct ligation, rats with biliary cirrhosis exhibited increased extravascular leakage of 125I-albumin in lung (p < 0.001) and kidney (p < 0.01) but not in heart or brain. In contrast, in cholestatic rats 10 days after bile duct ligation, only the kidney albumin leak was significantly increased (p < 0.01). Tissue thromboxane B2 levels, measured with an enzyme immunoassay, were increased in lung, kidney and liver of cirrhotic and cholestatic rats. To determine whether thromboxane A2 contributes to the vascular permeability defects in cirrhosis, we pretreated cirrhotic rats with the thromboxane synthase inhibitor dazoxiben (10 mg/kg intraperitoneally every 8 hr) for 20 hr before assessment of vascular permeability. Dazoxiben blocked the increase in thromboxane B2 level in lung but not in kidney and lowered the lung but not the kidney albumin leak index. In cholestatic rats given a higher dose of dazoxiben (40 mg/kg intraperitoneally every 8 hr) for 20 hr, the kidney thromboxane B2 level but not albumin leak was significantly lowered. We conclude that chronic biliary obstruction in rats leads to increased vascular permeability in selected extrahepatic organs and that thromboxane A2 contributes to the vascular permeability increase in the lung. Whether thromboxane A2 plays a role in renal albumin leakage will require further study.

6-Ketoprostaglandin F1 alpha↗
PubMed1993

Hyperglucagonemia and hyperdynamic circulation in rats with biliary cirrhosis.

Glucagon, a hormone with a potent vasodilatory action, has been suggested to play a role in the hyperkinetic circulation in animals with portocaval shunts and chronic portal venous stenosis; however, its role in cirrhosis has not been examined. We tested the hypothesis that increased levels of circulating glucagon contribute to the hyperdynamic circulatory state found in rats with biliary cirrhosis. Compared with plasma glucagon levels in sham-operated controls, glucagon levels, measured by radioimmunoassay, were significantly increased in chronic bile duct-ligated (5 to 6 weeks) cirrhotic rats (603 +/- 107 pg/ml vs 197 +/- 11 pg/ml, p < 0.001) but not in acute bile duct-ligated (10 days) cholestatic rats (310 +/- 55 pg/ml). Unanesthetized, catheter-implanted cirrhotic--but not cholestatic--rats exhibited a hyperdynamic circulatory state with increased cardiac index and decreased systemic vascular resistance. The plasma glucagon level correlated with cardiac index (r = 0.62, p < 0.01) and systemic vascular resistance (r = -0.54, p < 0.05). In addition, cirrhotic rats showed depressed hypoxic pulmonary vasoconstriction that was correlated with increased plasma glucagon level (r = -0.68, p < 0.01). We conclude that circulating glucagon is increased in rats with biliary cirrhosis and that hyperglucagonemia may contribute to the observed systemic hyperdynamic circulatory state and the loss of hypoxic pulmonary vasoconstriction in these rats.

Animals↗
PubMed1992

Role of eicosanoids in staphylococcal alpha-toxin-induced lung injury in the rat.

We investigated the role of arachidonic acid-derived eicosanoids in staphylococcal alpha-toxin (alpha-T)-induced lung injury. Bolus injection of 200 and 500 micrograms alpha-T into isolated perfused rat lungs resulted in increased pulmonary perfusion pressure followed by lung weight gain. Inhibition of pressure change with papaverine (10(-4) M) failed to abolish lung edema. Furthermore, alpha-T increased the permeability-surface area product in papaverine-treated lungs and caused marked endothelial cell injury and interstitial edema as documented by electron microscopy. alpha-T dose dependently increased lung tissue thromboxane B2 (TxB2) levels and leukotriene C4 levels. In lungs given 0, 200, and 500 micrograms of alpha-T, TxB2 (in micrograms/g wet lung) values were 16.3 +/- 2.8, 25.0 +/- 3.0, and 54.2 +/- 6.2; and leukotriene C4 values were 4.6 +/- 1.1, 6.7 +/- 1.2, and 22.1 +/- 3.8, respectively. Inhibition of cyclooxygenase enzyme with indomethacin (10(-5) M) or lipoxygenase enzyme with 2(12-hydroxydodeca-5,10-dinyl)-3,5,6-trimethyl-1,4-benzoq uin one (AA861, 10(-5) M) attenuated the vasoconstriction and prevented lung edema due to low dose (200 micrograms) but not high dose (500 micrograms) alpha-T. The protective effect of these inhibitors on lung edema is in part due to decreases in alpha-T-stimulated venoconstriction because alpha-T-induced increase in lung microvascular pressure was attenuated by indomethacin and AA861 pretreatment. We conclude that both eicosanoid-dependent and eicosanoid-independent mechanisms contribute to alpha-T-induced lung edema in the rat.

Animals↗
PubMed1992

Intact lung cytochrome P-450 is not required for hypoxic pulmonary vasoconstriction.

Lung cytochrome P-450 has been suggested to play a role in hypoxic pulmonary vasoconstriction. We reexamined this hypothesis using specific suicide substrate inhibitors of cytochrome P-450, 1-aminobenzotriazole (1-ABT), and chloramphenicol. In isolated, blood-perfused rat lungs, 1-ABT (0.5 mg/ml) and chloramphenicol (1 mg/ml) inhibited lung microsomal cytochrome P-450 (ethoxycoumarin O-deethylase) activity to 24 and 44% of control, respectively, and blunted hypoxia and angiotensin II-induced vasoconstriction. The depression of vascular contraction by 1-ABT was not due to an effect on calcium channels, since similar concentrations of 1-ABT had no inhibitory activity on electrical field-stimulated contractile response in rabbit papillary muscle strips. However, when 1-ABT was washed out of the lung after preincubation, the vascular reactivity to hypoxia and angiotensin II was restored despite persistent depression of lung cytochrome P-450 activity to 26% of control values. In isolated rat aortic and pulmonary arterial rings, addition of 1-ABT or metyrapone to the organ bath acutely reversed norepinephrine-induced contraction but preincubation with 1-ABT, metyrapone, or chloramphenicol had no effect on subsequent norepinephrine contractions. We conclude that 1-ABT inhibited lung vascular reactivity by a mechanism independent of cytochrome P-450 inhibition or calcium channel blockade and that an intact lung cytochrome P-450 system is not required for hypoxic pulmonary vasoconstriction in rat lungs.

Angiotensin II↗