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11.
Summary— KR31080 (2-butyl-5-methyl-6-(1-oxopyridin-2-yl)-3-[[2'-(1H-tetrazol-5-yl) biphenyl-4-yl]methyl]-3H-imidazo[4,5-b] pyridine) is a potent inhibitor of angiotensin type 1 (AT1 ) receptors in rabbit aorta and human recombinant AT1 receptors. In the isolated rabbit thoracic aorta, KR31080 caused a nonparallel shift to the right of the concentration-response curves to angiotensin II (All) with decreased maximal response (pD'2 = 10.1 ± 0.1), but had no effect on the contractile response induced by norepinephrine. KR31080 inhibited specific [125 I]AII binding to rabbit aortic membranes (AT, receptors) and [125 I][Sar1 , Ile8 ]AII binding to human recombinant AT1 receptors in a concentration-dependent manner with IC50 values of 0.84 ± 0.08 nM and 1.92 ± 0.15 nM, respectively, but did not inhibit specific [125 I)AII binding to bovine cerebellum membranes (ÀT2 receptors). In the Scatchard analysis, KR31080 interacted with rabbit aortic AT1 receptors in a competitive manner, similar to losartan. These results demonstrate that KR31080 is a potent and AT1 selective angiotensin receptor antagonist which exerts a competitive antagonism in the [125 I]AII binding assay and insurmountable AT1 receptor antagonism in the functional study. 相似文献
12.
Andressa A.F.L. Maciel Reinaldo B. Ori Manuel B. Braga-Neto Andra B. Braga Eunice B. Carvalho Herene B.M. Lucena Gerly A.C. Brito Richard L. Guerrant Aldo A.M. Lima 《Toxicon》2007,50(8):1027-1040
Vitamin A (retinol), a fat-soluble vitamin, is an essential nutrient for the normal functioning of the visual system, epithelial cell integrity and growth, immunity, and reproduction. Our group has investigated the effect of high doses of oral vitamin A on early childhood diarrhea in our prospective community-based studies from Northeast Brazil and found a beneficial role in reducing the mean duration but not incidence of diarrheal episodes. In this study, we explored the role of retinol supplementation in intestinal cell lines following Clostridium difficile toxin A (TxA) challenge. C. difficile is the most common anaerobic pathogen borne with antibiotic-borne diarrhea and pseudomembranous colitis. Since retinol is critical for the integrity of tight junctions and to modulate the cell cycle, we have focused on changes in transepithelial electrical resistance (TEER) in Caco-2, a more differentiated intestinal cell line, and on models of cell proliferation, migration and viability in IEC-6 cells, an undifferentiated crypt cell line, following TxA injury. In this model, retinol therapy reduced apoptosis, improved cell migration and proliferation, and prevented the reduction in TEER, following C. difficile TxA challenge in a glutamine-free medium. These results suggest the role of retinol in protecting intestinal epithelial barrier function from C. difficile TxA enterotoxic damage. 相似文献
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Kyu-Won Shim Tae-Gon Kim Chang-Ok Suh Jae-Ho Cho Chul-Joo Yoo Joong-Uhn Choi Jung-Hee Kim Dong-Seok Kim 《Child's nervous system》2007,23(10):1155-1161
Object A radiation dose of 40–50 Gy is able to produce a cure rate of more than 90% in intracranial pure germinoma. However, many
attempts have been made to reduce the dose and volume of radiation without compromising the disease control rate because of
the toxicity of irradiation. This retrospective study is intended to provide the physician with an appropriate therapeutic
strategy.
Materials and methods We reviewed a series of 10 recurrent germinomas among 117 germinomas diagnosed histologically or clinically between 1979 and
2002. These patients involved underwent three different treatment modalities; radiation alone (N = 71), chemotherapy alone (N = 9), and combined therapy (N = 37). The 10-year overall and relapse-free survival rates were 97 and 93% in the radiation alone group, 89 and 67% in the
chemotherapy alone group, and 92 and 92% in the combined therapy group, respectively. As expected, both radiation therapy
and combined therapy were effective in controlling the disease. Tumor recurrence was closely related to the volume of radiation
but not to the dose of radiation. If the tumor bed and craniospinal axis were fully covered, the radiation dose might be reduced.
Chemotherapy alone showed earlier recurrence and a higher tumor recurrence rate. In the case of combined therapy, chemotherapy
was useful in reducing the radiation dose but revealed some toxicity (death of two patients).
Conclusions The investigation of a possible further dose reduction seems worthwhile. Radiation therapy alone with a dose of less than
40 Gy should be compared with ongoing chemotherapeutic protocols combined with low-dose irradiation. 相似文献
15.
Hyo-Chang Kim Seok-Gu Kang Pil-Woo Huh Do Sung Yoo Kyoung Suok Cho Dal Soo Kim 《Journal of clinical neuroscience》2007,14(11):1135-1139
Pituitary abscess is a rare and potentially lethal condition. Pituitary abscess in a pregnant woman has not been previously described. A 38-year-old pregnant woman (34 weeks gestation) with a pituitary mass complained of a progressive headache and sudden visual impairment. She was afebrile and had no inflammatory symptoms on admission. On MRI, the preoperative diagnosis was pituitary adenoma with sphenoid sinusitis. She underwent an uncomplicated transsphenoidal procedure for removal of the pituitary mass. The next day, labor commenced and a healthy preterm baby was delivered. Pathologic examination of the intrasellar mass showed polymorphonuclear cells, debris and no tumor cells. The sellar contents were cultured and Streptococcus viridans was grown. To our knowledge this is the first case of pituitary abscess reported during pregnancy. Although the patient was pregnant, the transsphenoidal approach was safe for the mother and the fetus. Surgical drainage and antibiotic therapy are required for the definitive treatment of this condition. 相似文献
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Airway hyperresponsiveness (AHR) is a characteristic feature of asthma, but is also frequently demonstrated by children and adults with chronic obstructive lung diseases. AHR is usually measured by bronchial challenges using direct or indirect stimuli. The aim of this study was to compare these two types of bronchial challenge in children with post-infectious bronchiolitis obliterans (BO). Methacholine and adenosine 5'-monophosphate (AMP) challenges were used as tools for the evaluation of AHR to direct and indirect stimuli, respectively, in children with post-infectious BO (n = 28). These results were compared with those of asthmatic (n = 30) and control children (n = 25). Altogether, twenty-two patients (78.6%) with post-infectious BO were hyperreactive to methacholine with a provocative concentration causing a 20% fall in forced expiratory volume in one second (PC20) of <16 mg x mL(-1), but only six (21.4%) were hyperreactive to AMP with a PC20 of <200 mg x mL(-1). All patients with asthma responded positively to methacholine, and most (28, 93.3%) also responded positively to AMP. The majority of controls were insensitive to both challenges. Airway hyperresponsiveness to methacholine is a frequent, but by no means universal, finding in children with post-infectious bronchiolitis obliterans, but is usually not accompanied by airway hyperresponsiveness to adenosine 5'-monophosphate. This finding suggests that airway hyperresponsiveness in patients with post-infectious bronchiolitis obliterans has characteristics that differ from those of asthmatic subjects. 相似文献
20.
To elucidate the mechanisms by which thiamine deficiency affects hepatic microsomal monooxygenase activities, the effect of thiamine deficiency on two constitutive cytochrome P450 isozymes, P450IIE1 and P450IIC11, was investigated, using weanling male Sprague-Dawley rats. The clinical signs of thiamine deficiency were apparent after feeding a thiamine-deficient diet for 3 weeks. Thiamine deficiency caused an increase in P450IIE1, which was determined by N-nitrosodimethylamine demethylase assay and immunoquantitation of P450IIE1. This increase in the P450IIE1 level was mainly attributed to thiamine deficiency per se but not to dietary restriction. Ketone bodies were not elevated in thiamine-deficient rats, whereas ketone bodies were elevated and may have served as inducing factors in calorically restricted pair-fed animals. Injections of pyruvate or pyrithiamine in addition to thiamine deficiency did not potentiate the induction effect. On the other hand, thiamine deficiency did not affect the level of P450IIC11 during the 3 weeks of feeding the thiamine-deficient diet. In addition, thiamine deficiency increased cytosolic glutathione S-transferase activity but not steroid isomerase activity. The present study demonstrates the specificity of thiamine deficiency per se in the induction of P450IIE1 which does not involve an increase in the ketone body level. 相似文献