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Benzo[a]pyrene at an environmentally relevant dose is slowly absorbed by, and extensively metabolized in, tracheal epithelium 总被引:2,自引:0,他引:2
Gerde P; Muggenburg BA; Thornton-Manning JR; Lewis JL; Pyon KH; Dahl AR 《Carcinogenesis》1997,18(9):1825-1832
While tobacco smoke has been conclusively identified as a lung carcinogen,
there is much debate over which smoke constituent(s) are primarily
responsible for its carcinogenicity. Previous studies in our laboratory
suggested that highly lipophilic carcinogens are slowly absorbed in the
thicker epithelium of the conducting airways, potentially allowing for
substantial local metabolism. The bioactivation of polycyclic aromatic
hydrocarbons in airway epithelium may, hence, be important in tobacco
smoke-induced carcinogenesis. In the present study, the hypothesis of slow
absorption and substantial local metabolic activation of highly lipophilic
carcinogen in airway epithelium was tested in dogs. A single dose of
tritiated benzo[a]pyrene (BaP) dissolved in a saline/phospholipid
suspension was instilled in the trachea, just anterior to the carina. At
intervals of a few minutes up to 30 min over a 3-h period, blood samples
were drawn from the azygous vein, which drains the area around the point of
instillation, and from the systemic circulation. Tissue samples were taken
at the end of the experiment. The concentration of BaP with depth into the
tracheal mucosa was determined with autoradiography. BaP was slowly
absorbed into the trachea with a half-time of approximately 73 min, which
is consistent with diffusion-limited passage through the epithelium and
lead to local doses in the tracheal epithelium that were more than a
1000-fold those of other tissues. The long retention of BaP in the
epithelium provided the local metabolizing enzymes with high substrate
levels over a long period, resulting in extensive metabolism. At 3 h after
the exposure, 23% of the BaP-equivalent activity remained in the tracheal
mucosa. Of this fraction, 13% was parent compound, 28% was organic
extractable, 31% was water-soluble, and 28-7% of the instilled dose was
bound to tracheal tissues. These results explain the tendency of highly
lipophilic carcinogens, such as BaP, to induce tumors at the site of entry
and, furthermore, indicate that the highly lipophilic components of tobacco
smoke and polluted air may be the most important contributors to lung
tumors of the conducting airways.
相似文献
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Pedersen LM Terslev L SŁrensen PG Stokholm KH 《Medical oncology (Northwood, London, England)》2000,17(2):117-122
Transcapillary escape rate of albumin was determined in 22 patients with different malignancies. In addition, urinary albumin
excretion rate was measured in 24-h urine samples using a sensitive immunoassay. Increased urinary albumin excretion was defined
as ≥20 μg/min according to conventional standards. Renal glomerular filtration and tubular function was estimated by51Cr-EDTA plasma clearance and urinary beta 2-microglobulin, respectively. Median urinary albumin excretion rate was 15.0 μg/min
(range 6–510 μg/min) and the frequency of increased urinary albumin excretion was 41%. This agrees with other studies showing
increased albuminuria in several types of malignant diseases. Patients with advanced disease (tumour, node, metastasis (TNM)
stage II–IV) had a significantly higher urinary albumin excretion rate than patients with localized disease (TNM stage I).
Serum creatinine, glomerular filtration rate and urinary beta 2-microglobulin were all within normal limits. Median transcapillary
escape rate of albumin was 5.5%/h (range 2–8%/h) and this level is comparable with values in healthy subjects. There was no
significant difference in transcapillary escape rate between patients with elevated urinary albumin excretion and the normoalbuminuric
group. Median value of the absolut outflux of albumin was 10.6 g/h with similar levels in patients with increased urinary
albumin excretion and patients with normoalbuminuria. Our results indicate a high prevalence of minor glomerular dysfunction
with a slightly elevated urinary albumin excretion in patients with malignancies. The normal endothelial function, as estimated
by the transcapillary escape rate of albumin, suggests an overal unaffected capillary permeability and increased urinary albumin
loss appears to be an isolated renal phenomenon in cancer patients. 相似文献
35.
OBJECTIVE: To determine whether children's food consumption is increased by the size of the group of children in which they are eating. DESIGN: Crossover study. SETTING: University based preschool. PARTICIPANTS: 54 children, aged 2.5-6.5 years. INTERVENTIONS: Each child ate a standardised snack in a group of three children, and in a group of nine children. MAIN OUTCOME MEASURES: Amount each individual child consumed, in grams. RESULTS: Amount eaten and snack duration were correlated (r = 0.71). The association between group size and amount eaten differed in the short (<11.4 min) versus the long (> or =11.4 min) snacks (p = 0.02 for the interaction between group size and snack duration). During short snacks, there was no effect of group size on amount eaten (16.7 (SD 11) g eaten in small groups vs 15.1 (6.6) g eaten in large groups, p = 0.42). During long snacks, large group size increased the amount eaten (34.5 (16) vs 26.5 (13.8), p = 0.02). The group size effect was partially explained by a shorter latency to begin eating, a faster eating rate and reduced social interaction in larger groups. CONCLUSIONS: Children consumed 30% more food when eating in a group of nine children than when eating in a group of three children during longer snacks. Social facilitation of food consumption operates in preschool-aged children. The group size effect merits consideration in creating eating behaviour interventions. 相似文献
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Flexible tantalum stents implanted in aortas and iliac arteries: effects in normal canines 总被引:2,自引:0,他引:2
Barth KH; Virmani R; Strecker EP; Savin MA; Lindisch D; Matsumoto AH; Teitelbaum GP 《Radiology》1990,175(1):91-96
Vascular endoprostheses made of knitted tantalum wire and expanded over angioplasty balloons were placed into aortas or iliac arteries of 14 normal dogs. Twelve stents were placed into the infrarenal abdominal aorta and two stents in the left common iliac arteries by the left carotid artery approach. To firmly expand the stent against the vascular wall, nominal stent sizes 0.5-1.0 mm larger than the measured arterial diameter were required. Arteriography performed at specified follow-up intervals showed no evidence of thrombi or emboli; all side branches (lumbar arteries) covered by the stents remained patent. Vascular diameter decreased minimally at 8 and 26 weeks, associated with histopathologic evidence of neointimal buildup. This buildup was highest at 8 weeks (mean, 313 microns) and was slightly less at 26 weeks (mean, 223 microns). Almost complete coverage by endothelium was seen as early as 3 weeks. It is concluded that the flexible tantalum wire stents are well tolerated by the arterial wall and become quickly endothelialized. No excessive neointimal buildup was observed during the 6-month study. 相似文献