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  • 1
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background  Evidence suggests that small airways contribute to clinically significant processes in asthma. Cysteinyl leukotrienes (CysLTs) are considered to be pivotal mediators in the pathogenesis of asthma. Montelukast (MK), a specific CysLT1 receptor antagonist, is metabolized in two main hydroxylated metabolites (termed M5 and M6, respectively).Objectives  The aims of this study were to compare the responsiveness of small and large human bronchi to the three CysLTs, to evaluate the antagonist activity of MK, M5 and M6 in these preparations of human bronchi, and to characterize the CysLT receptors involved in the contractile response.Methods and results  In isolated small bronchus (i.d. 0.5–2 mm), the potencies (−log molar EC50) of LTC4, LTD4 and LTE4 were 9.3 (n=11), 9.1 (n=30) and 8.4 (n=14), respectively. The three CysLTs were about 30-fold more potent in small bronchi than in larger bronchi (i.d. 4–6 mm). In small bronchi, MK significantly shifted to the right the CysLT concentration–effect curves with pA2 values against LTC4, LTD4 and LTE4 of 9.1 (n=3), 9.0 (n=11) and 8.7 (n=5), respectively. The antagonist potencies of M6 and M5 were similar to MK and fivefold lower, respectively. A similar activity of MK against the three CysLTs suggested that CysLT1 receptors are involved in the contraction of human bronchus. Analysis by RT-PCR also indicated that human bronchus mainly expressed CysLT1 receptors.Conclusion  MK exerts a potent antagonist activity against the particularly potent constricting effects of CysLTs in isolated human small bronchi, which only expressed the CysLT1 receptor subtype. The metabolites of MK are also potent in vitro antagonists, but may not participate in the therapeutic activity of MK due to their low plasma concentrations in patients treated with the recommended dose of MK.
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  • 2
    ISSN: 1550-7408
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology
    Notes: . Trypanosoma cruzi trypomastigotes treated with phosphatidylinositol-specific phospholipase C (PI-PLC) in vitro are rapidly induced to differentiate into round forms. Using confocal microscopy, we were able to show that trypomastigotes treated with PI-PLC initiate the process of flagellum remodeling by 30 sec after contact with the enzyme and amastigote-like forms are detected as early as 10 min after PI-PLC treatment. Scanning and transmission electron microscopy indicate that trypomastigotes undergo a previously undescribed process of flagellum circularization and internalization. Analysis of the flagellar complex with monoclonal antibody 4D9 shows heterogeneous labeling among the parasites, suggesting a remodeling of these molecules. After PI-PLC treatment, parasites rapidly lose the surface marker Ssp-3 and 24 h post-treatment they begin to exhibit a circular nucleus and a rod-shaped kinetoplast. By flow cytometry analysis and confocal microscopy, the Ssp-4 amastigote-specific epitope can be detected on the parasite surface. This indicates that the release of trypomastigote GPI-anchored molecules by exogenous PI-PLC in vitro can trigger morphological changes.
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  • 3
    ISSN: 1438-1435
    Keywords: Key words Gastrointestinal tract, perforation – Pneumoperitoneum – Helical computed tomography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: To determine the value of helical CT in a consecutive series of elderly patients referred with clinically suspected gastrointestinal perforation. Methods: Our series comprised 34 consecutive elderly patients (mean age: 68 years) presenting with acute abdominal symptoms potentially suggestive of gastrointestinal perforation. All the patients were prospectively subjected to abdominal computed tomography (CT). On helical CT, the presence of free air was considered diagnostic of gastrointestinal perforation. Other findings such as intraperitoneal free fluid, thickening of bowel wall, streaky density within the mesentery, “dirty fat” sign, and focal collection of extraluminal fecal matter (“dirty mass”) were considered indirect findings of perforation. Results: At surgery, the following sites of perforation were found: duodenum (38.2 %), stomach (29.4 %), ileum (8.8 %), sigmoid colon (8.8 %), rectum (5.8 %), and jejunum, appendix, and transverse colon (2.9 % of cases each). CT demonstrated the presence of free air in 94.1 % of cases; intraperitoneal free fluid was present in 76.4 % of patients and thickening of bowel wall in 50 %. Streaky density within the mesentery was found in one patient. Conclusion: CT is a reliable diagnostic method by which to assess gastrointestinal perforation, because it provides excellent contrast resolution to depict the presence of even small amounts of free air in the abdomen. This is particularly helpful where elderly patients are concerned.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Emergency radiology 7 (2000), S. 263-267 
    ISSN: 1438-1435
    Keywords: Key words Gastrointestinal tract, perforation – Pneumoperitoneum – Ultrasound
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: To investigate the spectrum of US findings as encountered in a consecutive series of patients referred with clinically suspected gastrointestinal perforation. Methods: Seventy-two consecutive patients (mean age: 42.9 years) with clinically suspected gastrointestinal perforation were prospectively examined with abdominal ultrasound (US). The US examinations were all performed by a certified senior radiologist, who was blind to other imaging findings. Patients were screened for the presence of free intraperitoneal gas (characteristic comet-tail artifacts, ring-down artifacts, and the “shifting phenomenon” were our diagnostic indicators of pneumoperitoneum). Other signs potentially suggestive of gastrointestinal perforation were also looked for, including free intraperitoneal fluid, thickening of bowel walls, gallbladder walls, gastric walls, or duodenal walls, or local peritoneal inflammation. Patients with equivocal or inconclusive findings on US were submitted to abdominal computed tomography (CT) 10–15 min after US examinations. Results: Of the 72 patients prospectively examined by US, 63 (87.5 %) underwent subsequent emergent surgery within next 2 days. A gastrointestinal perforation was found in all the 63 patients referred for operative treatment: overall, 41 gastroduodenal and 22 intestinal perforations were found. On US, in the 41 patients with surgically proven gastroduodenal perforation, the most common finding was free intraperitoneal gas (28/41, 68.3 %). The 13/41 patients (31.7 %) without evidence of free gas on US underwent preoperative abdominal CT assessment, which allowed the correct diagnosis of gastroduodenal perforation in 12/13 cases. In the 22 patients with surgically proven intestinal perforation the most common finding detected on US was free intraperitoneal fluid (14/22, 63.6 %); sonographic evidence of free intraperitoneal gas was seen in only 8/22 patients (36.4 %). The 14/22 patients (63.6 %) without free gas on US underwent preoperative abdominal CT assessment, which allowed the diagnosis of intestinal perforation in 12/14 cases. Conclusion: US examinations allow very rapid screening of patients referred with clinically suspected gastrointestinal perforation and for triage of patients who are to undergo more invasive imaging tests.
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  • 5
    ISSN: 1573-5168
    Keywords: TEM ; mitochondria-rich cells ; cortisol ; Na+ ; K+-ATPase ; osmoregulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The aim of this work was to determine the effects of supplemental dietary sodium chloride on salt water acclimation of tilapia Oreochromis niloticus. Fish were fed a basal diet supplemented with NaCl (8%) during three weeks in fresh water (FW) and then transferred to salt water (SW) at 15 and 20‰. Changes in plasma osmolality, chloride ion concentration (Cl−), plasma level of cortisol and gill Na+, K+-ATPase activity were measured at 6, 12, 24, 48, 72 and 168 h after transfer to 15‰SW, while the higher strength SW group (20‰) was only monitored up to 24 h. Morphological changes in the gill mitochondria-rich (MR) cells were examined in relation to environmental salinity. The changes associated with dietary NaCl were sporadic and of small magnitude. The plasma osmolality and Cl− increased immediately after transfer up to 12–24 h, but fish fed dietary salt (S) showed lower values than the control group (C). The S group showed higher plasma levels of cortisol than the control, which maintained its initial levels during the experiment. Gill Na+, K+-ATPase activity of the S group began to increase in the first hours after transfer, reaching maximum at 12 h and returned to basal level at 24 h, while the control group maintained basal levels. The differences between gill Na+, K+-ATPase activity of S and C fish were significant (p 〈 0.05) at 12 h. Transmission electron microscopy (TEM) revealed that MR cells in SW show more mitochondria and a more developed tubular system arising from the basolateral membrane. The MR cells of both groups frequently formed a multicellular complex in SW, consisting of a main MR and one or more accessory cells. Such complexes are rarely observed in FW. Some MR cells of fish fed supplemented dietary salt displayed convex apical membrane in FW.
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