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71.
Optimization of a previously disclosed sorbitol dehydrogenase inhibitor (SDI, II) for potency and duration of action was achieved by replacing the metabolically labile N,N-dimethylsulfamoyl group with a variety of heterocycles. Specifically, this effort led to a series of novel, in vitro potent SDIs with longer serum half-lives and acceptable in vivo activity in acutely diabetic rats (e.g., 62, 67, and 69). However, the desired in vivo potency in chronically diabetic rats, ED90 less than or equal to 5 mg/kg/day, was achieved only through further modification of the piperazine linker. Several members of this family, including 86, showed better than the targeted potency with ED90 values of 1-2 mg/kg/day. Compound 86 was further profiled and found to be a selective inhibitor of sorbitol dehydrogenase, with excellent pharmacodynamic/pharmacokinetic properties, demonstrating normalization of sciatic nerve fructose in a chronically diabetic rat model for approximately 17 h, when administered orally at a single dose of 2 mg/kg/day.  相似文献   
72.
Since human subjects and laboratory animals may develop impaired immune response during surgery and the postoperative period, efforts have been made to preserve normal immune functions following surgery by the administration of nutritional supplements and probiotics. The present study was designed to examine the effect of a new nutritional supplement, BIOcocktail, on immune parameters in mice exposed to surgery. Forty mice were assigned to 4 groups containing 10 animals each. Two control groups (with and without subsequent sham laparotomy) were given tap water for 45 min every day for 2 weeks. The remaining 2 groups, with and without laparotomy, received BIOcocktail given orally for the same period of time. The proliferative response of splenic cells (splenocytes) stimulated with phytohemagglutinin (PHA), concanavalin A (Con A) and lipopolysaccharide (LPS) was determined by [3H]thymidine uptake. Cytokine levels were measured in splenocyte supernatants and sera using enzyme-linked immunosorbent assay (ELISA) kits. Natural killer cell activity of splenocytes was evaluated by 51Cr-release assay. Laparotomy, without BIOcocktail administration, was followed by a decreased proliferative response of splenocytes to PHA, Con A, and LPS and an increase in interleukin (IL)-6 serum level. In addition, a decreased secretion of IL-1beta, IL-12 and tumor necrosis factor (TNF)-alpha by the splenocytes was observed. Mice treated with BIOcocktail before laparotomy maintained a preoperative level of splenocyte proliferative response and serum concentrations of IL-12. It is concluded that BIOcocktail administered to mice for 2 weeks before operation resulted in the preservation of T- and B-cell proliferative response to mitogens and in the prevention of postoperative decrease in IL-12 serum level.  相似文献   
73.
Actions of atrial natriuretic peptides on the kidney   总被引:1,自引:0,他引:1  
  相似文献   
74.
The acceptance of the semiallogeneic fetus within the maternal environment requires tolerance mechanisms not fully characterized yet. Normal pregnancy is known to be associated with a Th2 profile. Furthermore, T-regulatory cells were proposed to regulate the Th2/Th1 balance at early stages of pregnancy. Treg may avoid the shift to a Th1 profile preventing miscarriage. Accordingly, spontaneous abortion is characterized by a Th1 dominance and diminished levels of Tregulatory cells (Treg). The major aim of the present work was to investigate if pre-eclampsia, a late immunological complication of pregnancy, is characterized by similar hallmarks. Therefore, we measured the surface antigens CD4, CD25, CD8, CTLA4 (as well as the secretion of IL-10) in peripheral blood from patients suffering from pre-eclampsia (n = 8) and age-matched patients undergoing normal pregnancies (n = 9) by 4-colour flow-cytometry. We were not able to find any significant differences in the levels of CD4+, CD25+, CD8+, CTLA4, CD4+/CD25+, CD4+/CD25bright, CD4+/CTLA4, CD25+/CTLA4, CD4+/CD25+/CTLA4, CD8+/CD25+, CD8+/CTLA4 or CD8+/CD25+/CTLA4 cell subsets. Our data suggest that Treg may not participate in the onset of pre-eclampsia and suggest other regulatory mechanisms during late pregnancy.  相似文献   
75.
76.
从平贝母茎叶中分离的平贝啶甙的结构   总被引:2,自引:0,他引:2  
本文报道自平贝母(Fritillaria ussuriensis Maxim)的地上茎叶中分得一种新的甾体生物碱甙,定名为平贝啶甙(pingbeidinoside),mp 242~243.2℃[a]D25+6.9°(c 0.145,MeOH)。经IR,MS,1HNMR和13CNMR谱解析,推定其结构为3β,16α,20-三羟基-Δ5-22,26-缩亚胺胆甾烷-25-O-α-D-葡萄糖甙。  相似文献   
77.
Childhood scoliosis: MR imaging   总被引:2,自引:0,他引:2  
The spinal cords of 28 scoliosis patients between the ages of 1 month and 17 years were examined with magnetic resonance (MR) imaging. Complete visualization was obtained in all cases. In 15 patients (53%) neuropathologic abnormalities demonstrated by MR imaging significantly affected their clinical course, including tethered cords (n = 7), syringomyelia (n = 5), Arnold-Chiari I malformation (n = 4), spinal cord tumors (n = 2), Arnold-Chiari II malformation (n = 3), and diastematomyelia (n = 1). The advantages of MR imaging in the evaluation of the scoliotic spine in children include a high sensitivity for the occult conditions associated with scoliosis, good anatomic demonstration of the cord, and absence of bone artifacts. MR imaging is recommended as a primary imaging modality in scoliosis, following conventional radiography.  相似文献   
78.
Cyano and amidino flavans, isoflavans and 3(2H)-isoflavenes were synthesized in order to study their in vitro antirhino-virus activity, by comparison with the known corresponding chloro derivatives. The activity of the new compounds was evaluated on rhinovirus 1 B infected HeLa cell cultures by examining their ability to interfere with viral cytopathic effect and with plaque formation. It was found that generally the cyano derivatives behave like the chloro compounds, whereas the amidino derivatives show a lower activity, although always dependent on the position of substituent.  相似文献   
79.
Digital imaging of the chest   总被引:4,自引:0,他引:4  
During the past several years, image acquisition in nuclear medicine, computed tomography, ultrasonography, subtraction angiography, and magnetic resonance has been by digitization. Despite these advances, research in the development of digital imaging in conventional radiography has lagged behind. Although studies with a variety of digital techniques have been carried out on several fronts, we still do not possess a method that has captured the imagination of the majority of radiologists and other physicians to a point where it could replace conventional screen-film imaging. This article reviews the current status and general principles of the technology, focusing on the four digital radiographic techniques that have shown the greatest promise - film digitization, an image intensifier - based system, photostimulable phosphor plates, and a scanned projection system. The physical aspects of each of the four systems and the clinical results that have been reported to date, as well as the advantages and disadvantages of each system, are presented.  相似文献   
80.
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