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The bioavailability of nifedipine in man is highly variable. This may be partly due to its poor aqueous solubility (5–6 µg/ml over pH 2.2–10.0, as determined in this laboratory). We initiated this study to examine the enhancement of aqueous nifedipine solubility via complexation. A series of substituted aromatic ligands was studied to identify those structural features important for complexation with nifedipine. The studies were performed at 25°C employing the solubility technique, using pH 2.2 or 7.0 buffers at an ionic strength of 0.25 M. The apparent equilibrium complexation constants for the 1:1 and/or 1:2 complexes were determined, where appropriate. A linear free-energy approach was used to relate K
1:1 with Hammett's sigma () and fractional partition coefficient () parameters. The following correlation was obtained: log (K
l:l/K
o = 0.31 + 0.l0 + 0.36 (r
2 = 0.86, P < 0.003, N = 9), where K
o is the complexation constant for phenol. Statistical analyses showed that was more important than in affecting nifedipine complexation. The exact location of this interaction on the nifedipine molecule is undefined at present. 相似文献
54.
The potential of binary mixtures of propylene glycol–water, ethanol–water, and polyethylene glycol 400–water to cause skeletal muscle damage (myotoxicity) following intramuscular injection was examined with an in vitro model using the isolated rat muscle. At moderate concentrations (20–40%, v/v) of the organic cosolvent, the order of myotoxicity was propylene glycol > ethanol polyethylene glycol 400. The in vitro results were then compared with in vivo toxicity in rabbits after injection of normal saline, 40% (v/v) polyethylene glycol 400, 40% (v/v) propylene glycol, indocyanine green in normal saline, and indocyanine green in 40% (v/v) propylene glycol. Employing the area under the creatine kinase activity curve from 0 to 72 hr as the index of skeletal muscle damage, an excellent in vitro–in vivo correlation was observed. The basic myotoxicity relationships obtained from the binary cosolvent systems were then used to examine the myotoxicity of ternary organic cosolvent mixtures. Several mixed solvent systems with the same theoretical molar solubilization power for a model compound, diazepam, were selected to determine (1) if myotoxicity can be reduced by changing the composition of the ternary mixtures and (2) if myotoxicity of the individual components is additive. For the solvent systems containing propylene glycol, ethanol, and water, the total myotoxicity equaled the sum of the individual myotoxicity of each component. In contrast, for the solvent systems containing polyethylene glycol 400, the total myotoxicity was only half of the sum of individual toxicities. These results suggest that polyethylene glycol 400 in mixed cosolvent systems might have a protective effect on the myotoxicity generated by intramuscular injections. 相似文献
55.
Identification of Potential Diagnostic and Vaccine Candidates of Helicobacter pylori by Two-Dimensional Gel Electrophoresis, Sequence Analysis, and Serum Profiling 总被引:3,自引:0,他引:3 下载免费PDF全文
C. Patrick McAtee Moon Young Lim Kevin Fung Mark Velligan Kirk Fry Theresa Chow Douglas E. Berg 《Clinical and Vaccine Immunology : CVI》1998,5(4):537-542
There is great interest in characterizing the proteins of the gastric pathogen Helicobacter pylori, especially those to which humans respond immunologically, because of the potential importance of such proteins in diagnosis and vaccine development. Two-dimensional gel electrophoresis was used to separate and identify potential antigens of H. pylori ATCC 43504. Over 30 proteins were reactive in Western blots with pooled sera from 14 infected patients. These proteins were analyzed by N-terminal sequence analysis. Fourteen proteins were determined to be distinct from any proteins previously described from H. pylori; the others were previously isolated and characterized proteins. Analysis of eight distinct H. pylori strains showed that most of these antigens were produced by all of the strains. We propose that collection of new antigens such as those recognized here will be useful in serologic tests for detecting and monitoring H. pylori infection and may also serve as potential targets for antimicrobial agent or vaccine development. 相似文献
56.
Corrigan C Mallett K Ying S Roberts D Parikh A Scadding G Lee T 《The Journal of allergy and clinical immunology》2005,115(2):316-322
BACKGROUND: Cysteinyl leukotrienes play a disease-regulating role in rhinosinusitis and asthma, particularly aspirin-sensitive disease. They act through 2 G-protein coupled receptors termed cysteinyl leukotriene type 1 receptor (cysLT 1 ) and cysteinyl leukotriene type 2 receptor (cysLT 2 ). We previously compared expression of cysLT 1 on mucosal leukocytes in patients with aspirin-sensitive and aspirin-tolerant rhinosinusitis. OBJECTIVE: To compare expression of cysLT 1 and cysLT 2 on leukocytes, mucus glands, and epithelium in 32 patients with chronic polypoid rhinosinusitis (21 aspirin-sensitive, 11 aspirin-tolerant) and 9 normal controls. METHODS: Total numbers of CD45 + leukocytes, percentages of these cells expressing cysLT 1 or cysLT 2 , and percentages of the total epithelial and glandular areas expressing cysLT 1 or cysLT 2 were measured in sections of nasal biopsies by using immunohistochemistry and image analysis. RESULTS: The percentages of mucosal CD45 + leukocytes expressing cysLT 1 were significantly ( P < .0001) elevated in the aspirin-sensitive but not the aspirin-tolerant patients compared with the controls. In contrast, the percentages of leukocytes expressing cysLT 2 did not differ significantly in the 3 groups. On epithelial and glandular cells, expression of cysLT 2 significantly exceeded that of cysLT 1 in both the patients with rhinosinusitis and the controls ( P < or = .004), although there was no significant difference in the expression of either receptor in the patients with rhinosinusitis (aspirin-sensitive or aspirin-tolerant) and the controls. CONCLUSION: Although cysLT 1 expression predominates on inflammatory leukocytes in patients with aspirin-sensitive rhinosinusitis, the effects of cysteinyl leukotrienes on glands and epithelium may be mediated predominantly through cysLT 2. This has potentially important therapeutic implications. 相似文献
57.
58.
WSX-1 is required for resistance to Trypanosoma cruzi infection by regulation of proinflammatory cytokine production 总被引:6,自引:0,他引:6
Hamano S Himeno K Miyazaki Y Ishii K Yamanaka A Takeda A Zhang M Hisaeda H Mak TW Yoshimura A Yoshida H 《Immunity》2003,19(5):657-667
WSX-1 is a class I cytokine receptor with homology to the IL-12 receptors and is essential for resistance to Leishmania major infection. In the present study, we demonstrated that WSX-1 was also required for resistance to Trypanosoma cruzi. WSX-1-/- mice exhibited prolonged parasitemia, severe liver injury, and increased mortality over wild-type mice. WSX-1-/- splenocytes produced enhanced levels of Th2 cytokines, which were responsible for the prolonged parasitemia. Massive necroinflammatory lesions were observed in the liver of infected WSX-1-/- mice, and IFN-gamma that was overproduced in WSX-1-/- mice compared with wild-type mice was responsible for the lesions. In addition, vast amounts of various proinflammatory cytokines, including IL-6 and TNF-alpha, were produced by liver mononuclear cells in WSX-1-/- mice. Thus, during T. cruzi infection, WSX-1 suppresses liver injury by regulating production of proinflammatory cytokines, while controlling parasitemia by suppression of Th2 responses, demonstrating its novel role as an inhibitory regulator of cytokine production. 相似文献
59.
Synergistic effect of IL-4 and TNF-alpha in the induction of monocytic differentiation of a mouse myeloid leukaemic cell line (WEHI-3B JCS). 总被引:1,自引:0,他引:1 下载免费PDF全文
We have previously shown that non-cytotoxic concentrations (600-1200 U/ml) of recombinant mouse tumour necrosis factor-alpha (TNF-alpha) can induce differentiation of a subclone (JCS) of the WEHI-3B myelomonocytic leukaemia cell line into mature cells with the characteristics of macrophages. In the present study, the effects of recombinant mouse interleukin-4 (IL-4), either alone or in combination with mouse TNF-alpha, on the growth and differentiation of JCS cells were examined. IL-4 alone (20-5000 U/ml) inhibited the growth of JCS cells in a dose-dependent manner but did not induce cell differentiation. However, combinations of IL-4 and TNF-alpha acted in synergy to inhibit cell proliferation and induce monocytic differentiation of JCS cells, as shown by increased expression of the macrophage differentiation antigens (F4/80, Mac-1), stimulation of phagocytic activity, induction of non-specific esterase and NBT-reducing activities, increased plastic adherence and morphological criteria. Similar synergistic interactions were also shown by human TNF-alpha and mouse IL-4, indicating that TNF-alpha might exert its effects through the low-affinity (p55) TNF receptors. Moreover, the clonogenicity of JCS cells in vitro and their tumorigenicity in vivo were significantly reduced by combined TNF-alpha and IL-4 treatment. Our results indicate that TNF-alpha can act as a differential signal for JCS cells and that its effects are modulated by IL-4. Therefore, the combination of TNF-alpha and IL-4 may be useful in the treatment of some forms of myelomonocytic leukaemia. 相似文献
60.
AIMS: To define epidemiology, clinical disease, and outcome of gemella bacteraemia by 16S rRNA gene sequencing. To examine the usefulness of the Vitek, API, and ATB systems in identifying two gemella species. METHODS: All alpha haemolytic streptococci other than Streptococcus pneumoniae isolated from blood cultures during a six year period were identified by conventional biochemical methods, the Vitek system, and the API system. 16S rRNA gene sequencing was performed on all isolates identified by both kits as gemella with >or= 95% confidence or by either kit as any bacterial species with < 95% confidence. The ATB expression system was used to identify the two isolates that were defined as gemella species by 16S rRNA gene sequencing. RESULTS: Of the 302 alpha haemolytic streptococci other than S pneumoniae isolated, one was identified as Gemella morbillorum, and another as Gemella haemolysans by 16S rRNA gene sequencing. The patient with monomicrobial G morbillorum bacteraemia was a 66 year old man with community acquired infective endocarditis with septic thromboemboli. The patient with G haemolysans bacteraemia was a 41 year old woman with hospital acquired polymicrobial bacteraemia during the neutropenic period of an autologous bone marrow transplant for non-Hodgkin's lymphoma, the first case of its kind in the English literature. The API and ATB expression systems only identified the second strain as G haemolysans at 94% and 99% confidence, respectively, whereas the Vitek system identified none of the two strains correctly at > 70% confidence. CONCLUSIONS: Gemella bacteraemia is uncommon. 16S rRNA gene sequencing is the method of choice for identification of gemella and gemella-like isolates. 相似文献