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991.
BACKGROUND: Endothelins have been implicated in gastric mucosal damage in a variety of animal models. Exogenous ET-1 and ET-3 are causally associated with experimental gastric ulcers. Furthermore, clinical reports also show elevated plasma and gastric mucosal endothelin-1 levels in patients suffering from peptic ulcers. AIM: To study the possibility that endothelin receptor antagonists may have beneficial effects and prevent the development of gastric ulcers. We have tested in rats the orally-active endothelin antagonist bosentan (Ro 47-0203) and Ro 48-5695, which is 10-30 times more potent than bosentan on endothelin receptors. METHODS: Water immersion restrained stress (WIRS) and indomethacin were used to provoke gastric mucosal damage. Endothelin receptor antagonists were administered orally prior to the induction of gastric damage. The gastric lesion index (mm), assessed macroscopically, and myeloperoxidase (MPO) activity were used as markers of the extent of mucosal injury. RESULTS: Bosentan at 100 and 30 mg/kg administered orally caused attenuation of gastric damage in the WIRS model by 58% and 42%, respectively. Bosentan also caused complete reduction of MPO activity. In indomethacin-induced gastric damage, 100 mg/kg bosentan attenuated gastric damage by 45% and 61% as measured by the gastric lesion index and MPO activity respectively. Ro 48-5695 was at least 30 times more potent than bosentan in reducing indomethacin-induced mucosal damage and at 3 mg/kg, caused a decrease of 49% in the gastric lesion index and a reduction in MPO activity of 41%. Bosentan and Ro 48-5695 possess weak antisecretory properties as tested in the mouse gastric gland assay, than cannot, alone, account for their anti-ulcer properties. CONCLUSIONS: Both endothelin receptor antagonists prevented the development of gastric mucosal injury in the rat. Disturbances in the gastric microcirculation are responsible for the development of experimental gastric ulcers. The anti-ulcer properties of these two endothelin antagonists suggest possible new therapeutic approaches to controlling gastric inflammation. 相似文献
992.
Pai RG Jintapakorn W Tanimoto M Cao QL Pandian N Shah PM 《Echocardiography (Mount Kisco, N.Y.)》1996,13(6):613-622
Accurate determination of left ventricular (LV) volume has important therapeutic and prognostic implications in patients with cardiac disease. Volume estimations by two-dimensional techniques are not very accurate due to geometric assumptions. OBJECTIVES: To validate LV volume determinations by a new transesophageal three-dimensional echocardiographic technique. We performed three-dimensional reconstruction of the LV using an echo-computed tomographic (CT) technique based on serial pullback parallel slice imaging technique in both in vitro and in vivo settings. Fourteen latex balloons with various sizes (30-235 mL) and shapes (conical, pear shaped, round, elliptical, and aneurysms in various locations) filled with known volumes of water were imaged in a water bath. From the static three-dimensional image, the LV long axis was defined and the LV was sectioned perpendicular to this axis into 2-mm slices. The volume of each slice was calculated with the observer blinded to the actual volume as the product of the slice thickness and the manually traced perimeter of the slice and the LV volume as the sum of the volumes of the slices (Simpson's method). The calculated LV volume closely correlated with the actual volume (r = 0.99, P < 0.0001, calculated volume = 1.06x - 11.3, Deltavolume = -5.7 +/- 10.0 cc). Using the same system, transesophageal echocardiographic (TEE) images of the LV were obtained in 15 patients gated to respiration and ECG. Satisfactory dynamic three-dimensional reconstruction of the LV was possible in ten patients. The three-dimensional LV volumes (systolic and diastolic) using Simpson's method correlated well with those obtained from biplane or multiplane TEE images using the area length method (r = 0.89, p < 0.0001, y = 12.7 + 0.84x, Deltavolume = 1.3 +/- 18.1 cc). The LV major-axis diameters by the two methods showed very close correlations as well (r = 0.86, P < 0.0001, y = 19 + 0.74x, Deltadiameter = 1.0 +/- 7.2 mm). We conclude that three-dimensional LV volume calculation by the echo-CT technique is intrinsically sound, is independent of LV geometry, and with some limitations, is applicable in vivo. (ECHOCARDIOGRAPHY, Volume 13, November 1996) 相似文献
993.
A. A. Podowski M. A. Q. Khan 《Archives of environmental contamination and toxicology》1996,30(1):21-29
The radioactivity on adding 14C-Hexachlorocyclopentadiene (Hex) to water (7 7gmg/L) decreased by 18% on Day 2 and by 31 to 55% by Day 42. On Day 42, the radioactivity remaining in water consisted of apolar (petroleum ether-extractable), polar (ethyl acetate-extractable), and hydrophilic hydrolysis products with Hex amounting to only 8% of the total radioactivity. The time for Hex to reach 50, 10, and 5% of its initial concentration was estimated to be about 4, 27, and 40 days, respectively. The hydrolysis rate constant compared to 4×103 hr–1 as reported in literature. The apolar radioactivity (25% of total) consisted of Hex and a major product as judged by gas chromatography (GC). The polar products resolved into 10 and hydrophilics into 14 different compounds as examined by thinlayer chromatography.The photolysis of Hex in acetone occurred very rapidly (t1/2=<1 day) with no trace of Hex after 15 days. Most of these products were more polar than Hex as examined by GC. These products on thin-layer chromatography (TLC) separated into two major zones. Further TLC of each of these zones showed products of one zone to resemble those of aqueous hydrolysis. The other zone represented apolar products which resolved into three peaks by HPLC, the major one of these appeared to have an empirical formula of C6Cl7O (m/e=408) as analyzed by GCMS.The 8-h photolysis products' mixture had an LT50 to goldfish Carassius auratus of 22 h compared to 15 h for Hex. The 96-h LT50 value of the 15-day photolysis products' mixture was 2,300 compared with 119 g/L for Hex. Thus, Hex in water as well as on exposure to light breaks down to less toxic products. 相似文献
994.
Chan CC Factor V Li Q Nagy P Peng B Thorgeirsson SS 《Ocular immunology and inflammation》1996,4(4):183-191
Transforming growth factor-beta (TGFsZ) is a potent regulator of cellular growth and immune function. The authors studied ocular histology and endotoxin-induced uveitis in a TGF-sZ(1) transgenic (Tg) murine model. TGF-sZ(1) Tg mice were generated by micro injecting a gene constructed by fusing the mouse albumin enhancer/promoter and porcine TGF-sZ(1) cDNA. The eyes of Tg mice from two to 14 weeks of age were studied histologically. Tg mice, two to five weeks of age exhibited mild fragmentation of the lens fibers and retinal edema. No pathology was found from six to ten weeks of age, however, a progressive increased frequency of cataract was observed from 11 to 14 weeks of age. Plasma TGF-sZ(1) levels were much higher in Tg mice than age-matched wild type control littermates (wt). Endotoxin-induced uveitis (EIU) in six-to eight-week-old Tg and wt mice was induced by footpad injection of lipopolysaccharide (LPS). Mice were euthanized 24 hr after LPS injection, the eyes were collected for histology and serum assayed for IL-6 and TGF-sZ(1). There was a decrease in the mean numbers of infiltrating cells in Tg mice compared to wt mice. Serum IL-6 and TGF-sZ(1) were much higher in Tg mice. The authors concluded that expression of the TGF-sZ(1) transgene in the eyes may have effect on lens growth. Overexpression of TGF-sZ(1) results in little or no effect on the development of EIU. 相似文献
995.
A methanolic extract of the whole plant of Elephantopus mollis was found to contain lupeol, lupeol acetate, epifriedelinol, molephantin, and 2-de-ethoxy-2-methoxyphantomolin, as well as a new sesquiterpene lactone determined to be 2-de-ethoxy-2-hydroxyphantomolin. 相似文献
996.
The aerial parts of Artemisia mongolica afforded the eudesmane derivative ludovicin B, two coumarins, umbelliferone and esculetin, two methoxylated flavones, eupatilin and pectolinarigenin, as well as a new eudesmane sesquiterpene, 6alpha,8alpha-dihydroxyisocostic acid methyl ester. Structures were elucidated by highfield 1D and 2D NMR techniques. 相似文献
997.
Honn KV Aref A Chen YQ Cher ML Crissman JD Forman JD Gao X Grignon D Hussain M Porter AT Pontes JE Powell I Redman B Sakr W Severson R Tang DG Wood DP 《Pathology oncology research : POR》1996,2(1-2):98-109
Rates of prostate cancer (PCa) have increased so dramatically over the last decade that the age adjusted incidence rate for PCa is now greater than that any other cancer among men in the United States. This review, published as a three part series, provides a state-of-art assessment of the PCa problem in its divergent aspects.Part 1 covers epidemiology, incidence and progression. Several epidemiological studies have demostrated that first degree male relatives of men with PCa are at increased risk of developing the disease. Familial and genetic factors as well as medical, anthropometric, dietary, hormonal and occupational factors involved in PCa are discussed. Postmortem examination of the prostate in men without evidence of PCa documented a high frequency of adenocarcinoma. Latent disease occurred as early as the second decade of life. Although there is no significant difference in incidence between Caucasian and African-American males, high grade prostatic intraepithelial neoplasia (HGPIN) is higher in the latter group. While dietary fat, androgens and certain environmental factors may be determinants for PCa, the exact mechanism of tumorigenesis is still relatively unknown. The current thinking of the role of genomic instability, chromosomal alterations, tumor suppressor genes and the androgen receptor are explored. 相似文献
998.
Lam T. H.; Jiang C. Q.; Liu W. W.; Zhang W. S.; He J. M.; Zhu C. Q. 《Occupational medicine (Oxford, England)》1996,46(5):351-355
This cross-sectional study aimed to describe the pattern ofsmoking in relation to occupational hazard exposure in a workingpopulation in Guangzhou, China. In 1994, data on smoking andoccupational hazard exposure from occupational health recordsof 8,304 subjects aged 35 years or older from 47 randomly selectedfactories were studied. About 49% of the men and 55% of thewomen were exposed to dust, chemicals or other hazards. Theprevalence of smoking was 56.1% in men and in women. The prevalenceof smoking in men was higher in those who were younger, withprimary education or who were workers. In women, those who wereolder, with primary education or in management jobs had highersmoking prevalence. In men and women, subjects who were exposedto occupational hazards had higher smoking prevalence: the highest(71.6%) was found in male workers exposed to dust. Urgent tobaccocontrol measures are needed to prevent the epidemic of smoking-relatedand occupation-related diseases in the workplace in China. 相似文献
999.
Compliance with oral corticosteroids during steroid trials in chronic airways obstruction. 总被引:1,自引:0,他引:1
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BACKGROUND: Corticosteroid trials are an important part of the assessment of patients with chronic airways obstruction, but false negative results will occur if the treatment is not taken. To determine compliance low dose phenobarbitone has been used as a marker. METHODS: Thirty six patients referred to a chest clinic for assessment of their airways obstruction were studied. They were instructed to take eight capsules (each containing 5 mg prednisolone and 0.5 mg phenobarbitone) per day for two weeks. The response was assessed by home peak flow monitoring and clinic spirometric tests. Plasma phenobarbitone levels were measured after the trial to enable calculation of the dose to plasma concentration ratio (level to dose ratio, LDR) and the result was compared with the reference range for fully compliant individuals. RESULTS: Five patients defaulted from follow up, 23 had LDR values within the expected range, and eight had low LDR values consistent with poor compliance. The nine patients with steroid responsive disease (> 20% improvement in peak flow or spirometric parameters) all had LDR values in the expected range. CONCLUSION: Excluding those who defaulted whose compliance must be questionable, eight (26%) patients did not fully comply with the steroid trial. Not all patients who fail to respond to a two week home steroid trial have a steroid "unresponsive" disease. 相似文献
1000.
(=) 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) has been the most widely used pharmacological tool in research on 5-HT(1A) receptor function. In the present study, the behavioural effects of 8-OH-DPAT entantiomers were compared using an ethological version of the murine elevated plus-maze test. Subcutaneous pretreatment (-20min) with R(+)-8-OH-DPAT (0.03-1.0mg/kg) produced a pronounced; and dose-dependent behavioural suppression (decreased open/closed/total arm entries and increased nonexploratory behaviours). In contrast, over the same dose range, S(-)-8-OH-DPAT reduced several ethological indices of anxiety without altering the majority of conventional parameters or general activity levels, e.g. arm entries and per cent time measures, as well as head dipping. Findings are discussed in relation to differences in the intrinsic activity of 8-OH-DPAT isomers at 5-HT(1A) sites and the putative role of these receptors in anxiety-related processes. The differential behavioural profiles of 8-OH-DPAT enantiomers suggest that racemic 8-OH-DPAT may not be an ideal tool for research on the behavioural pharmacology of 5-HT(1A) receptors. 相似文献