Remodeling of rabbit abdominal aorta and Cx43 gap junctions after stent placement: effect of balloon injury plus cholesterol-enriched diet.

AIM: To examine the effect of stenting and cholesterol-enriched diet (CED) on vascular remodeling, including the expression of connexin43 (Cx43) gap junctions in smooth muscle cells (SMC). METHODS: Rabbits abdominal aortae were either implanted stent made of 316 stainless steel (group 1) or denuded followed by stent placement 28 days later (groups 2 and 3). Animals were given normal chow except those of group 3, which were fed CED after the denudation. Eight weeks later, the development of neointima and the expression of connexin43 (Cx43) were examined. In parallel, human aortic SMC were grown on 316 stainless steel or treated with C-reactive protein (CRP) followed by analysis of Cx43. RESULTS: The results showed that, serum CRP levels became transiently elevated after denudation and stent implantation. For the stented aortic segments, the dimensions of neointima were group 3 > group 2 > group 1 (P<0.05). In groups 1 and 2, Cx43 gap junctions are less in amount in neointima of the stented segment, compared to the unstented upstream neointima or medial layer (all P<0.01). In culture experiments, Cx43 in SMC grown on stent material was up-regulated in growth medium but down-regulated in differentiation medium, and CRP did not affect Cx43 expression. CONCLUSION: Vascular remodeling post stent implantation varied according to the presence of balloon injury, CED, or both. Cx43 expression in SMC is altered after exposure to stent and the regulation depended on the milieu.

Trace metals in different species of mollusca, water and sediments from Taiwan coastal area.

Since October 1994, a long-term program of Asia/Pacific Mussel Watch: Taiwan Regional Studies has been carried out. The results indicate that trace metal contents in mollusca varied among 30 different species and the environments (water and sediments) along the Taiwan coast. The orders of bioaccumulation of trace metals in mollusca were: Cu (over 200 microg/g), Thais clavigera > Isognomon legumen > Clibanarius rivescens > Crassostrea gigas; Zn (over 700 microg/g), Moruta granulata > C. gigas > Asiatica cypraea arabica > T. clavigera; Cd (over 5 microg/g), Trochus hanleyanus > Acanthopleura japonica > Nerita albicilla > Patella flexuosa; Pb (over 2 microg/g), P. flexuosa > C. gigas > T. hanleyanus > T. clavigera > C. gigas > Capiyulum mitella; Ni (over 10 microg/g), Meretrix lusoria > Philine sp. > Littoraria scabra > Tridacna squamosa > T. hanleyanus; Cr (over 30 microg/g), Littoraria undulata > T. hanleyanus > N. albicilla > Nerita chamaelor > M. granulata; As (over 20 microg/g), Perna viridis > L. scabra; and Sn (over 5 microg/g), P. viridis > L. undulata> C. mitella> C. gigas. Their seasonal and regional variations as well as their correlation are evaluated and discussed.

Organotins and imposex in the rock shell, Thais clavigera, from oyster mariculture areas in Taiwan.

The amounts of organotin compounds such as butyltins [sigma BTs: tributyl- (TBT), dibutyl- (DBT), monobutyl- (MBT)] and phenyltins [sigma PhTs: triphenyl- (TPhT), diphenyl- (DPhT) and monophenyl- (MPhT)] in rock shells, Thais clavigera, from the northern (Shiangsan), central (Lukang) and southern (Chiku) Taiwan oyster mariculture areas varied with season and location. High values of sigma BTs (mainly TBT) and low values of sigma PhTs (mainly TPhT) were found during winter (January 1999) at Shiangsan, while high amounts of sigma PhTs (mainly TPhT) and low sigma BTs (mainly TBT) were found during summer (August 1998) at Lukang. The snails were also affected by imposex. Imposex at Shiangsan, Lukang and Chiku increased from 67.1, 59.3 and 36.7% in summer to 100, 100 and 80% in winter, respectively. Relative penis size indices similar trend at Chiku site. No male displayed rock shells were found at Shiangsan and Lukang in winter. Linear correlations between pseudopenis length versus TBT (r = 0.7655, P < 0.001), DBT (r = 0.4253, P < 0.05), MBT (r = 0.5865, P < 0.01) and TPhT (r = -0.6160, P < 0.01) were obtained significant. Among 200 samples, significant positive correlations between length (pseudopenis/shell) ratio of female versus TBT (r = 0.6944, P < 0.005) and sigma BTs (r = 0.6413, r < 0.01) were also observed. The weak correlations between length (pseudopenis/shell) ratio of female versus DBT (r = 0.3085) and MBT (r = 0.4240, P < 0.1) and TPhT (-0.4917, P < 0.05; negative correlation) could indicate that DBT, MBT and TPhT have little or no effect on the development of imposex in rock shells.

Mussel watch: a review of Cu and other metals in various marine organisms in Taiwan, 1991-98.

This study presents the distribution of Cu, Zn, Pb, Cd, Hg and As in various marine organisms collected along the western coast of Taiwan from 1991 to 1998, and also evaluates the time variation of Cu in oysters before (1980-85) and after (1986-98) the "green oyster" incident. The results show that relatively high geometric mean (GM) concentrations of Cu, Zn, Pb, Cd, As and Hg were generally found in Crassostrea gigas (Cu=229 microg/g, Zn=783 microg/g), Gomphina aeguialtera (Pb=30.3 microg/g), Tegillarca granosa (Cd=2.85 microg/g), Thais clavigera (As=96.9 microg/g) and Parapenaeopsis cornuta (Hg=1.35 microg/g), respectively. Especially, maximum Cu and Zn concentrations (GM=229 and 783 microg/g, respectively) in oysters (C. gigas) from different culture areas were much higher than those of the other organisms by about 1.13-458 and 2.40-63.7 times, respectively. Similarly, rock-shells (Thais clavigera) had a high capacity for accumulating Cu (GM=202 microg/g) and Zn (GM=326 microg/g) under the same physico-chemical conditions. The highest GM Cu and Zn concentrations of 1108 (range from 113 to 2806) and 1567 (range from 303 to 3593) microg/g were obtained in oysters from the Hsiangshan coastal area, one of the most important oyster culture areas in Taiwan. However, the highest GM Cd and As concentrations of 6.82 and 19.3 microg/g were found in oysters from the Machu Islands. Mean Cu concentrations in the oysters from the Erhjin Chi estuary declined from 2194+/-212 microg/g in 1986-90 to 545 microg/g (GM) in 1991-96. In the Hsiganshan area, GM Cu concentrations of 909 microg/g (1991-96) and 1351 microg/g (1997-98) in oysters were significantly higher than those of 201 microg/g (1980-85) and 682 microg/g (1986-90). The gradually increasing levels of Cu and Zn in the oysters from the Hsiangshan area have been observed year by year.

Estimation of metal and organochlorine pesticide exposures and potential health threat by consumption of oysters in Taiwan.

Pollutant concentrations detected in oysters from 12 different culture areas of Taiwan (especially for the Hsiangshan area and the Machu Islands) from 1991-98 were evaluated to investigate potential carcinogenic (inorganic As and organochlorine pesticides) and non-carcinogenic (Cu, Zn, Cd and inorganic As) risk to the public from ingestion of the oysters. The highest geometric mean (GM) Cu and Zn concentrations of 1108 (range 113-2806) and 1567 (range 303-3593) microg/g dry weight were obtained in oysters from the Hsiangshan coastal area. The maximum GM Cd and As concentrations of 6.82 and 19.3 microg/g dry weight were found in oysters from the Machu Islands area. The p,p'-DDE values range from not detectable in Penghu Islands' oysters to 164 ng/g dry weight in Machu Islands' oysters. The highest tDDT (sum of p,p'-DDE, p,p'-DDD and p,p'-DDT) concentrations of 337 and 340 ng/g dry weight were found in oysters from Kimmen and Machu Islands, respectively. A calculated target hazard quotient (THQ; daily intake/reference dose) of 11.4 (based on 139 g oysters/day) for Cu caused by consuming oysters from the Hsiangshan area is higher than that from other areas (range 0.124-5.95). The highest average Cu intake from Hsiangshan's oysters for individuals is 11.4 times (i.e. THQ=11.4) more than that of reference dose (40 microg/kg/day). However, the maximum THQ values for Cd and As caused by consuming oysters collected from the Machu Islands were 5.57 and 2.63 for Cd and As, respectively. Generally, the results of THQ showed that if only the maximally exposed individuals were considered, the value of 65.4% for oyster was higher than 1.0 in comparison with reference dose. All cancer risk estimates for inorganic As from consuming oysters were higher than 10(-6) (range from 128x10(-6) to 509x10(-6) for maximally exposed individuals and range from 17.1x10(-6) to 68.0x10(-6) for typically exposed individuals, respectively); that is the risk of the lower end of the range of acceptable risk. The highest risk estimate for inorganic As was 509x10(-6) for consumption of oysters by Machu Islands' residents. The lifetime cancer risks of 19.0x10(-6) for tDDT by consuming oysters from the Machu Islands was higher than those from the Penghu Islands (0.37x10(-6)). Therefore, the sum of lifetime cancer risks for tDDT and inorganic As had the highest risks (total risk=528x10(-6)) of consuming oysters from the Machu Islands. Furthermore, a 10(-6) upper limit on lifetime risk as the health protection standard would require maximum oyster consumption rates of approximately 0.26 g/day.

Estimation of target hazard quotients and potential health risks for metals by consumption of seafood in Taiwan.

The purpose of this paper is to describe the impact of metal pollution on the main seafood and assess the potential health risk from consuming the contaminated seafood in Taiwan. The results of geometric mean (GM) metal concentrations in various seafood showed that the copper, zinc, and arsenic concentrations in oysters were significantly (p < 0.001) higher than those in the other seafood by about 1,057, 74.3, and 56.2 times, respectively. The green color found in the oysters was due to high GM copper and zinc concentrations of 909 (ranging from 113-2,805) and 1,293 (ranging from 303-3,593) microg/g dry wt, respectively. In addition, using a maximum consumption rate of 139 g/day of oysters for individuals, calculations yield target hazard quotients (daily intake/reference dose) of below 1 for cadmium and mercury and high values of 1.61, 9. 33, and 1.77 for inorganic arsenic, copper, and zinc in adults, respectively. The various lifetime cancer risks for inorganic arsenic (maximum exposed individuals risk ranging from 9.93 x 10(-6) to 3.11 x 10(-4)) might be caused by consuming different seafood in Taiwan. The highest risk estimate for inorganic arsenic was 5.10 x 10(-4) for consumption of oysters by Machu Islands residents. The long-term exposure of metals through consumption of oysters, especially for some high-risk groups, could be dangerous. Taking inorganic arsenic for example, a 10(-6) upper limit on lifetime risk as the health protection standard would require maximum oyster residue levels of approximately 0.0076-0.056 microg/g wet wt, for consumption rates of 139-18.6 g/d. In the light of known risks to public health, the government should issue an immediate warning to the public to refrain from eating all seafood harvested from the Taiwan coastal areas, especially the Hsiangshan area and the Machu Islands.

133Xenon ventilation scan as a functional assessment in bronchiectasis.

BACKGROUND: Mucus impaction in the airways impairs ventilation and exercise tolerance in patients with bronchiectasis. Parameters for evaluating the ventilatory dynamic change have been limited by variable cofactors. We developed a tool to evaluate the changes directly on images of a ventilation scan. MATERIALS AND METHODS: We used a 133Xenon ventilation washout scan to assess the time of half clearance (T1/2) of the regions of interest (ROIs) corrected by that of a control area (CA) as T1/2ROI/CA. We then compared the ventilation washout scan with high-resolution computer tomography (HRCT) scoring to assess the severity of bronchiectasis, as well as conducting 6-minute walking tests or spirometry for the evaluation of the clinical response to a 3-day course of chest physiotherapy. Nine patients with bronchiectasis and mucus hypersecretion were enrolled in this study. RESULTS: The functional impairments by mucus impaction or air trapping were well documented in the ventilation washout scan, which not only provided an anatomical image but also dynamic profiles. The ratios of T1/2ROI/CA were significantly correlated to the corresponding scoring of HRCT (3.45 +/- 0.85 vs 7.50 +/- 1.51, r2 = 0.61, p = 0.023, n = 8). The improvement in T1/2ROI/CA (from 3.45 +/- 0.85 to 2.60 +/- 0.59, p = 0.022, n = 9) was paralleled by an increase in the 6-minute walking test (from 310.4 +/- 43.2 m to 352.4 +/- 45.1 m, p = 0.028, n = 7). CONCLUSION: The 133Xenon scan may be used to evaluate the heterogeneity of ventilation abnormalities and the efficacy of clinical therapy directly in patients with bronchiectasis.

Relationship between copper speciation in sediments and bioaccumulation by marine bivalves of Taiwan.

This paper evaluates the relationships between copper species in sediments and accumulation by the purple clam (Hiatula diphos) and venus clam (Gomphina aeguilatera) collected from the field and culture (aquaculture) ponds in the polluted coastal area of Lukang, Taiwan. Sediment was sampled along with the molluscs, including oysters (Crassostrea gigas), purple clams (Hiatula diphos), rock-shells (Thais clavigera), venus clams (Gomphina aeguilatera), and hard clams (Meretrix lusoria), from two unique environments of Lukang during the period from August 1993 to July 1994. The data indicate that the total copper concentrations in sediments from culture ponds (185 microg g(-1)) was higher than those of the field (44.0 microg g(-1)). Copper species in sediments were analyzed by a sequential leaching technique. Results show that concentrations of various copper species in the sediments are in the range of 1.14 +/- 0.59 to 13.2 +/- 22.4 microg g(-1) and 0.36 +/- 0.24 to 133 +/- 36.7 microg g(-1) for the two environments, respectively. Also the exchangeable copper in sediment from culture ponds was 15 times higher than that from the field. In addition, the sum of exchangeable and copper carbonates had the highest percentages of copper in both the pond sediment (86.6 %) and the field sediment (50.7 %). Maximum copper concentrations (309 +/- 35.1 microg g(-1)) in oysters were much higher than those in the other benthic organisms by about 4-127 times. Similarly, the data also showed that copper concentrations in Thais clavigera were 12-32 times higher than those in other benthic organisms. Copper concentrations in various benthic organisms differed significantly (p < 0.05) from that in Thais clavigera. This capacity makes Thais clavigera a potential candidate for monitoring copper in marine sediments. In terms of copper species, the best correlation was generally obtained between copper carbonates in sediments and copper concentrations in Hiatula diphos (r = 0.886*). A strong multiple regression correlation (p < 0.05, r2 = 0.7894) also indicates that the copper carbonates may dominate as the available form of copper to Hiatula diphos from various environments in the Lukang coastal area under natural physicochemical conditions.

Species of copper and zinc in sediments collected from the antarctic ocean and the Taiwan Erhjin Chi coastal area.

The species of copper and zinc, such as bioexchangeable, skeletal, easily reducible (Fe and Mn oxides), moderately reducible (crystalline Mn oxide), organic combined with sulfides, and detritus with minerals, in mud and sand, separated from the surface Antarctic Ocean and the Taiwan Erhjin Chi coastal (including river and estuarine) sediments, have been analyzed by sequential leaching methods. Results show that in the Antarctic Ocean sediments, high concentrations of total copper (128 mg/kg) and zinc (458 mg/kg) were found in the high mud (99.09%) content samples compared with the low concentrations of total copper (83.8 mg/kg) and zinc (288 mg/kg) in low mud (51.69%) content samples. High concentrations of copper, zinc, manganese and iron are possibly due to the characteristics of manganese nodules, in which the species of copper and zinc are mainly contained in the crystalline Mn oxide phase. In the Taiwan Erhjin Chi coastal sediments, the total copper and zinc concentrations in mud and sand vary with season and location. High values were generally observed in the river sediments during the dry season, and low values were in the estuarine and coastal sediments during the heavy rainy season. High percentages of copper (as high as 49.4%) and zinc (as high as 76.7%) in mud and sand were in the bioexchangeable phase including the skeletal phase. This result might be correlated with the problems arising from human impact on copper and zinc as well as sewage pollution in Taiwan. In the organic combined phase, biogenic particulate matter related to higher primary productivity in the Antarctic Ocean is also discussed.

Effects of long-term Novacor artificial heart support on blood rheology.

This study presents characteristics of hemorheology for six patients during long-term support (85-144 days) on a Novacor left ventricular assist device (LVAD) as a bridge-to-cardiac transplantation. Results indicate that a certain "baseline" rheology can be identified in patients whose support was uneventful. However, in the patients who had one or more neurologic episodes during support, these events were associated with altered hemorheology, including increases in plasma and relative blood viscosity, and red cell rigidity.

Alterations in erythrocyte rheology in patients with severe peripheral vascular disease: 1. Cell volume dependence of erythrocyte rigidity.

The erythrocyte rigidity of patients suffering from severe peripheral vascular disease (PVD) was measured by a filtration method using 3 microns pore size filters. Filtration pressures for both PVD patients and normal subjects showed a cell volume dependency, and patient filtration pressures were normalized to cell volume to evaluate intrinsic, ie, nonvolume dependent, abnormalities in erythrocyte deformability. A significant (p less than 0.001) increase in cell rigidity was found in 44 of 54 PVD patients in comparison with volume-matched normal controls. No significant difference was found between patient mean corpusculer hemoglobin (MCH) and normal MCH at any given mean corpuscular volume (MCV), indicating that observed increases in erythrocyte rigidity are not attributable to changes in patient MCH. Therefore, the mechanism of increase in erythrocyte rigidity for PVD patients still needs further investigation into such parameters as levels of adenosine triphosphate,2,3-DPG, and membrane fluidity (calcium- and/or protein-binding membrane, cholesterol and phospholipid content of membrane, etc), as well as other aspects of erythrocyte physiology.

Interim use of Jarvik-7 and Novacor artificial heart: blood rheology and transient ischemic attacks (TIA's).

The rheological properties of blood were studied in patients supported by both the Jarvik-7 total artificial heart (TAH) and Novacor left ventricular assist device (LVAD) as a bridge to cardiac transplantation. Both groups of patients had abnormalities in blood rheology which differed according to the type of device implanted as well as on the clinical state of the patient. The rheology of individual patients correlated well with their clinical status and outcome, with incidences of TIA's and/or stroke being accompanied by marked increases in relative blood viscosity, erythrocyte rigidity, fibrinogen concentration and platelet aggregation in varying combination. Observed abnormalities in blood rheology were also crucial to thrombus formation on artificial heart valves as well. Our results show that the therapeutic management of rheological parameters should prove to be a unique and clinically rewarding approach to these patients.

Artificial heart. Hemorrheology and transient ischemic attacks.

Hemorrheology was studied in patients undergoing artificial heart support as a bridge-to-cardiac transplantation. Abnormal hemorrheology was seen in two patients, one on a Jarvik-7 total artificial heart, and the other on a Novacor left ventricular assist device. Both of these patients suffered neurologic episodes. The rheology of these two patients coincided well with their clinical status, and was accompanied by marked increases in relative blood viscosity, erythrocyte rigidity, fibrinogen concentration, and platelet aggregation. Results show that improving hemorrheology may be a beneficial avenue to pursue in preventing or treating transient ischemic attacks or other complications in patients during support with mechanical devices.

Green oysters caused by copper pollution on the Taiwan coast.

The first case of green oysters (Crassostrea gigas) broke out along the Charting mariculture area of south-western Taiwan in January 1986. The green color was found to be due to high copper content in the oyster tissue. Since then, a long-term survey around this area shows that total dissolved copper ranges from 4.99 to 23.6 microg/liter and particulate copper ranges from 1.09 to 5.51 microg/liter in sea-water. The green oysters collected from the Erhjin Chi estuary on 26 January, 1989 gave the highest copper content, 4401+/-79 ppm dry wt. Other green oyster cases were occasionally observed in the Hsiangsan and Anpin mariculture areas. Meanwhile, an experiment of copper accumulation in oysters was conducted at three stations (south-western Taiwan) for up to 90 days. Multiple regression analysis indicates that the food pathway may predominate in copper accumulation by green oysters. This bioaccumulation experiment shows that the total uptake of copper per oyster is an exponential function of exposure time for the first 2 weeks with an accumulation rate of 214 ppm Cu/day and then levels off. The average values of concentration factors for oysters (about 5 x 10(5)) were very close to steady-state values under the natural conditions at each station.

Characteristics of blood rheology in patients during Novacor left ventricular assist system support.

Blood rheologic properties were studied in 11 patients on Novacor LVAS support (1-126 days) as a bridge to transplantation. Overall, these patients showed slight increases in mean blood viscosity and red cell rigidity. Their mean plasma fibrinogen was in the upper normal range. However, the degree of rheologic change observed, and the individual factors affected most, were unique to each patient and hemorheologic results correlated well with the patient's clinical status.

Erythrocyte deformability in patients on left ventricular assist systems.

Preliminary hemorheologic studies using clinical filtration techniques on blood cell suspensions have suggested that changes in erythrocyte (RBC) deformability occur during left ventricular assist system (LVAS) support. In the biophysics literature, it is generally accepted that the elastic properties of the RBC membrane complex affect the microcirculatory deformability of the whole cell (cytoplasmic pathologies excepted). This paper compares single cell measurements of the surface shear elastic modulus, mu, of the RBC membrane complex (determined using micropipette aspiration) to available clinical filtration pressure data during Novacor LVAS support, over 33 and 126 days in four patients.

Clinical utilization of the artificial heart.

During the past 30 years the artificial heart has evolved from a bioengineering concept to clinical reality. To date four patients have had an artificial heart implanted as a permanent device, while over 150 artificial hearts have been utilized temporarily as a bridge to cardiac transplantation. Increased use of this device requires that a number of issues be critically addressed: (1) criteria for patient selection; (2) operative techniques for implantation including size of device and its position in the mediastinum; and (3) management of the patient in the intensive care unit (ICU), in particular, regimens of anticoagulation, assessment of adequacy of organ perfusion, and prevention of sepsis. This chapter is a discussion of these bioengineering and clinical concerns with respect to the Jarvik total artificial heart (TAH). Clinical data are presented which highlight the current problems with these devices and the areas of future research that need to be undertaken.

Design, synthesis, and testing of potential antisickling agents. 6. Rheologic studies with active phenoxy and benzyloxy acids.

In vitro rheologic studies have been performed with homozygous sickle erythrocytes in the presence of phenoxy and benzyloxy antigelling agents. The results correlate with those obtained previously from a standard hemoglobin S solubility assay (C-sat) that monitors the inhibition of hemoglobin S polymerization in solution. The order of activity of compounds in both studies was found to be about the same. The rheologic assay monitors the reduction in pressure (130 mm Hg sickled vs 9 mm Hg nonsickled) needed to push erythrocytes through a 5 micron filter. Among the drugs studied, the antilipidemic drug Clofibrate reduced the filtration pressure by as little as 9%, and a derivative of the diuretic agent ethacrynic acid (Merck-595, 595) reduced it by as much as 94%. Human Serum Albumin (HSA) (0.1% wt/vol) drastically reduced the activity of the noncovalently-acting aromatic acids by requiring at least three times the concentration of drug to obtain similar reductions in pressure. Two covalently-acting compounds, ethacrynic acid and Merck-595, 595, strongly increased the filterability of homozygous S erythrocytes at 1 and 3 mM drug concentrations even in the presence of HSA. No reason is given for the strong inhibitory effect of HSA at such high drug to HSA concentrations.