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1.
New monomers with sterically hindered free or blocked phenolic hydroxyl groups were used as starting compounds for the preparation of stable oxygen polyradicals. In this paper the synthesis of these monomers is described: 2,6-Di-(tert-butyl)-4-vinylphenol was obtained by decarboxylation of 3-[3,5-di-(tert-butyl)-4-hydroxyphenyl]acrylic acid in yields of 80–;90%. 2,6-Di-(tert-butyl)-4-isopropenylphenol was prepared from 3,5-di-(tert-butyl)-4-hydroxyphenyl methyl ketone and methyl iodide by a GRIGNARD reaction followed by the dehydration of 2-[3,5-di-(tert-butyl)-4-hydroxyphenyl]-2-propanol. 2,6-Di-(tert-butyl)-4-isopropenylphenyl methyl ether was obtained with 64% yield from 3,5-di-(tert-butyl)-4-methoxybenzonitrile by two consecutive GRIGNARD reactions with methyl iodide via the unknown compounds 3,5-di-(tert-butyl)-4-methoxyphenyl methyl ketone and 2-[3,5-di-(tert-butyl)-4-methoxyphenyl]-2-propanol, followed by dehydration of the tertiary alcohol with 89% phosphoric acid.  相似文献   
2.
Improved quality of life has gained importance over shortly lasting remissions in yet incurable metastatic breast cancer. Fractionation of drug administration is one of the possible approaches to reduce the concentration-dependent toxicity of anthracyclines. We evaluated the pharmacokinetics of 4-O-tetrahydropyranyladriamycin (THP-ADM) under weekly administration in patients with advanced breast cancer (dose escalation, from 20 to 27 mg/m2 THP-ADM). The concentration-time curves of THP-ADM in plasma were best described by an open three-compartment model [half-life of the first disposition phase (t1/2), 3.15 min; terminal elimination half-life (t 1/2), 13.9 h] with a mean area under the curve (AUC) of 12.2 ng h ml–1mg–1m–2, resulting in a mean plasma clearance of 86.91 h–1m–2. Metabolism included the formation of Adriamycin (ADM), Adriamycinol (ADM-OH), 13-dihydro-4-O-tetrahydropyranyladriamycin (THP-OH), 7-deoxyadriamycinone (7H-ADn), and 7-deoxy-13-dihydroadrimycinone (7H-ADn-OH), with maximal plasma concentrations ranging from 2.8 to 5.5 ng/ml. The mean total amount of cytotoxic anthracyclines excreted into urine, mainly as the parent drug, was 5% of the delivered dose. ADM and ADM-OH, but not the parent drug, were observed in urine at up to 4 weeks after the last therapeutic cycle. There was a significant correlation between the leukocyte nadir under therapy and the AUC of ADM-OH (r=0.800,P<0.05). Since no shift in the plasma kinetics was observed from the first to the sixth cycle, the favorable ratio of the AUCs of THP-ADM and ADM after fractionation of THP-ADM suggests lower toxic side effects attributable to ADM. This hypothesis was confirmed in a clinical study, where no severe cardiotoxicity and only mild alopecia were observed in 19 patients. Thus, pharmacokinetics studies might be helpful in both individualization of therapy with THP-ADM and optimization of the administration schedule.  相似文献   
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Primary drug resistance is a major problem in multiple myeloma, an incurable disease of the bone marrow. Cell adhesion-mediated drug resistance (CAM-DR) causes strong primary resistance. By coculturing multiple myeloma cells with bone marrow stromal cells (BMSCs), we observed a CAM-DR of about 50% to melphalan, treosulfan, doxorubicin, dexamethasone, and bortezomib, which was not reversed by secreted soluble factors. Targeting the adhesion molecules lymphocyte function-associated antigen 1 (LFA-1) and very late antigen 4 (VLA-4) by monoclonal antibodies or by the LFA-1 inhibitor LFA703 reduced CAM-DR significantly. Only statins such as simvastatin and lovastatin, however, were able to completely restore chemosensitivity. All these effects were not mediated by deadhesion or reduced secretion of interleukin 6. Targeting geranylgeranyl transferase (GGTase) and Rho kinase by specific inhibitors (GGTI-298 and Y-27632), but not inhibition of farnesyl transferase (FTase) by FTI-277, showed similar reduction of CAM-DR. Addition of geranylgeranyl pyrophosphate (GG-PP), but not of farnesyl pyrophosphate (F-PP), was able to inhibit simvastatin-induced CAM-DR reversal. Our data suggest that the 3-hydroxy-3-methylglutaryl-coenzyme-A (HMG-CoA)/GG-PP/Rho/Rho-kinase pathway mediates CAM-DR and that targeting this pathway may improve the efficacy of antimyeloma therapies by reduction of CAM-DR.  相似文献   
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Radiologic maxillary sinusitis is an important risk factor for development of bronchopneumonia in mechanically ventilated patients. Nitric oxide produced within the paranasal sinuses is considered to provide an antibacterial environment and to modulate mucociliary clearance function. We hypothesized that a reduced formation of nitric oxide might contribute to the compromised local host defense in radiologic maxillary sinusitis and measured nitric oxide levels directly within maxillary sinuses of septic patients with radiologic maxillary sinusitis (n = 11), whose sinuses were fenestrated to eliminate a possible septic focus. Data were compared with those of patients without airway inflammation (n = 11, control subjects). Despite local inflammation and infection, we found considerably lower maxillary nitric oxide levels than in control subjects (31 +/- 10 versus 2554 +/- 385 parts per billion, mean +/- standard error of the mean, p < 0.001). Consistently, immunohistochemical and in situ hybridization investigations revealed strongly reduced expression of inducible nitric oxide synthase. By applying ultrastructural immunolocalization, we identified cilia and microvilli of the maxillary sinus epithelium as the major nitric oxide production site in control subjects. Our findings provide evidence of markedly reduced nitric oxide production in maxillary sinuses of patients with radiologic maxillary sinusitis and sepsis, implicating impaired local host defense and an increased risk for secondary infections.  相似文献   
7.
Aim: Gender differences in morbidity have been widely confirmed in representative health surveys in North America and Europe. Significantly more women than men suffer from somatic complaints. It is less clear whether differences in symptom reporting provide an impact on health care utilization and to which degree psychosocial factors exhibit confounding influence. Methods: We analyzed data from a representative health examination survey in Germany with 7466 participants in the age range of 25 to 69 years. Results: The analysis confirmed an overall excess in female symptom reporting, both in the total sample (n = 7460; p 0.001) and in the healthy subsample (n = 906, p 0.01). Also, female utilization of medical services was higher (p 0.0001). A simultaneous age related increase in the prevalence of symptom reporting in both groups peaked in the age group of 55–59 years followed by a subsequent slight decrease in higher age groups whereas utilization steadily increased over the adult life span in both sexes. As expected, more medical utilization was associated with higher symptom reporting levels. Nevertheless, females constantly exhibited more medical utilization than males in all symptom reporting groups. Age and marital status had no univariate influence on symptom reporting whereas low social class status (p = 0.001), poor perceived/self assessed health (p < 0.0001), and high levels of chronic distress (p < 0.0001) were associated with more symptom reporting. In multivariate analysis, the female gender lost its significance on heightened symptom reporting. Poor perceived/self assessed health had the most pronounced impact on symptom count (F-value 59.1; p < 0.001). Conclusions: The present study confirms a female excess of symptom reporting and utilization of medical services. Nevertheless, symptom reporting and utilization are not closely related. The gender gap in symptom reporting may be largely explained by low social class status, high levels of chronic distress and poor perceived/self assessed health.  相似文献   
8.
Recombinant antibody (RAb) technology is expected to play an essential role in future food and environmental immunoanalysis. The RAb approach is not yet, however, considered as a standard method, mainly due to technical reasons. In order to establish a feasible protocol for the production of hapten specific RAbs, the essential steps of the procedure are considered in detail, especially the polymerase chain reaction amplification of antibody coding genes and the utilization of immunomagnetic selection of phages displaying selective RAbs. The synthesis of functional recombinant single‐chain Fv against s‐triazine herbicides is used as an example. Expressed RAbs are characterized by immunoassay. Although RAb‐based calibration curves were shifted toward higher concentrations by one order of magnitude, the cross‐reactivity pattern of RAbs corresponded to the original monoclonal antibodies. Sequences of different RAb clones derived from the same hybridoma line only differed in a single silent mutation. This confirms the reliability of the RAb procedure.  相似文献   
9.
Ohne ZusammenfassungDer Inhalt dieses Aufsatzes schließt sich dem ersten Teil eines in der Biologischen Gesellschaft Wien, vom Verfasser am 22. Mai 1925 gehaltenen Vortrages an.  相似文献   
10.
Fifty consecutive patients with acute pancreatitis were assessed with respect to a biliary origin of the disease. Endoscopie retrograde cholangiopancreaticography, surgery, and autopsy were used to define biliary pancreatitis. Ultrasound, computed tomography, and several laboratory tests (SGOT, SGPT, alkaline phosphatase, and bilirubin) were analyzed for their ability to detect a biliary origin of the disease. Ultrasound and computed tomography could not reliably make the diagnosis in the 10 patients found to have biliary disease. Receiver-operator-characteristic curves revealed that none of the laboratory tests assessed had sufficient sensitivity and specificity to determine the diagnosis, although all tests showed higher mean values in biliary pancreatitis. SGPT gave the best discrimination (positive predictive value 53%, negative predictive value 94%, cut off 40 Units/liter). Therefore, initial ERCP is suggested for a reliable diagnosis of biliary origin of acute pancreatitis.  相似文献   
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