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41.
Insulin resistance is common in patients with angina pectoris, a positive exercise electrocardiogram, and normal coronary angiograms (syndrome X). It is still not known whether insulin resistance affects the cardiac muscle itself and, if so, whether insulin resistance involves myocardial hemodynamics and energy metabolism. We investigated hemodynamics as well as metabolite exchanges across the heart and the forearm in eight patients with syndrome X and eight control subjects during a baseline period after an overnight fast and during a hyperinsulinemic-euglycemic clamp. Myocardial hemodynamics and metabolism were studied at rest, during pace stress, and in the recovery period after pacing. Neither coronary sinus blood flow nor forearm blood flow differed between the groups before and during the clamp. Whole body insulin-stimulated glucose uptake was decreased in the patients (15.6+/-2.1 vs. 23.1+/-2.0 micromol x kg-1 x min-1). Insulin-stimulated glucose uptake in the forearm and the cardiac muscle was equally reduced in the patients (46+/-5 and 48+/-5%). Myocardial glucose uptake correlated with total arterial delivery in the control subjects (r = 0.63, P < 0.01), but not in patients (r = 0.22, P = 0.13). Carbohydrate and lipid oxidation was similar in the two groups at rest, and changes during the clamp were not different in control subjects and patients either at rest, during pacing, or in the recovery period. Patients with syndrome X exhibit myocardial insulin resistance, but cardiac energy metabolism remains unaffected. In patients with syndrome X, insulin-stimulated glucose uptake is independent from myocardial blood flow.  相似文献   
42.
The CD9 antigen, a major platelet glycoprotein, is a member of the tetraspan superfamily. We show that treatment of K562 cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) which induces megakaryocytic differentiation, leads to a seven-fold increase in CD9 expression, which becomes associated with the integrin beta1, suggesting that it is functionally relevant. The upregulation of CD9 expression precedes the appearance of the megakaryocytic-specific marker GPIIb (CD41) as well as integrins beta3 (GPIIIa/CD61), alpha v (CD51) and VLA-2 (CD49b). Both GPIIb/IIIa expression and CD9 upregulation are dependent on protein kinase C (PKC) activation since they are blocked by the specific inhibitor GF109203X. Steady-state levels of CD9 and GPIIb mRNA were also measured by quantitative RT-PCR. Both messengers were detected on resting cells and were shown to accumulate during TPA treatment. However, the increase of the CD9 mRNA was detected much earlier than the increase of GPIIb mRNA (1-2 h vs 24-48 h). Using different constructs of the 5'-flanking domain of the CD9 gene cloned ahead of the CAT reporter gene, we could demonstrate that a responsive element was located in a 52 bp fragment of the promoter of the CD9 gene. Altogether, these data suggest that CD9 upregulation in the megakaryocytic lineage could occur at early stages of differentiation.  相似文献   
43.
    
The growth of microbial multidrug resistance is a problem in modern clinical medicine. Chemical modification of active pharmaceutical ingredients is an attractive strategy to improve their biopharmaceutical properties by increasing bioavailability and reducing drug toxicity. Conjugation of antimicrobial drugs with natural polysaccharides provides high efficiency of these systems due to targeted delivery, controlled drug release and reduced toxicity. This paper reports a two-step synthesis of colistin conjugates (CT) with succinyl chitosan (SucCS); first, we modified chitosan with succinyl anhydride to introduce a carboxyl function into the polymer molecule, which was then used for chemical grafting with amino groups of the peptide antibiotic CT using carbodiimide chemistry. The resulting polymeric delivery systems had a degree of substitution (DS) by CT of 3–8%, with conjugation efficiencies ranging from 54 to 100% and CT contents ranging from 130–318 μg/mg. The size of the obtained particles was 100–200 nm, and the ζ-potential varied from −22 to −28 mV. In vitro release studies at pH 7.4 demonstrated ultra-slow hydrolysis of amide bonds, with a CT release of 0.1–0.5% after 12 h; at pH 5.2, the hydrolysis rate slightly increased; however, it remained extremely low (1.5% of CT was released after 12 h). The antimicrobial activity of the conjugates depended on the DS. At DS 8%, the minimum inhibitory concentration (MIC) of the conjugate was equal to the MIC of native CT (1 µg/mL); at DS of 3 and 5%, the MIC increased 8-fold. In addition, the developed systems reduced CT nephrotoxicity by 20–60%; they also demonstrated the ability to reduce bacterial lipopolysaccharide-induced inflammation in vitro. Thus, these promising CT-SucCS conjugates are prospective for developing safe and effective nanoantibiotics.  相似文献   
44.
    
The ability to precisely control cell‐loaded material systems is essential for in vitro testing of novel therapeutics poised to advance to clinic. In this report, unique patterns of cell migration are devised into an in vitro gel‐in‐gel model for the purpose of obtaining cell response data to potentially therapeutic chemical agonists. The model consists of co‐cultures in a cell‐loaded microgel invading an acellular “sorting” gel. Material properties including biophysical and chemical compositions of the sorting gel are carefully controlled to guide a desired cell‐specific behavior, leading to massive tumor cell invasion by amoeboid migration mechanisms. Optical transparency enables straightforward and high‐throughput measurements of outgrowth response in the presence of either chemical and photoradiation therapy. Important dosing and drug sensitivity information are obtained with the gel‐in‐gel model using no more than a light microscope, without further need for arduous genomic or proteomic screening of the tissue samples.  相似文献   
45.
The post-penetrating keratoplasty (PK) corneal profile may be unpredictable and visual rehabilitation can be difficult. A case series of 11 such patients with flat corneal topography is presented and their management described. Suture removal may not provide a sufficient re-modelling effect to restore convexity of the cornea to enable satisfactory contact lens fitting and reverse geometry (RG) lenses have an important role.  相似文献   
46.
Suppose a configurationX consists ofn points lying on a circle of radiusr. If at most one of the edges joining neighboring points has length strictly greater thanr, then the Steiner treeS consists of all these edges with a longest edge removed. In order to showS is, in fact, just the minimal spanning treeT, a variational approach is used to show the Steiner ratio for this configuration is at least one and equals one only ifS andT coincide. The variational approach greatly reduces the number of possible Steiner trees that need to be considered.  相似文献   
47.
GB McCowage  J Kurtzberg  P Rubinstein 《Canadian Metallurgical Quarterly》1995,333(1):67; author reply 68-67; author reply 69
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48.
49.
That man most luckily forms his plan, among all the persons in Fortune's palace, who chooses a wheel befitting her wish (Machiavelli, quoted in Gilbert, 1989: 747).  相似文献   
50.
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