Compatibility and activity of aldesleukin (recombinant interleukin-2) in presence of selected drugs during simulated Y-site administration: evaluation of three methods

The compatibility and biological activity of aldesleukin (a form of recombinant interleukin-2) in the presence of selected i.v. drugs during simulated Y-site administration was studied. Five milliliters of aldesleukin 33,800 IU/mL in 5% dextrose injection was mixed in glass test tubes with 5 mL of each of 19 i.v. drugs prepared at concentrations used in routine clinical practice. The compatibility of the combinations was assessed by visual examination and spectrophotometry at 0, 0.5, 1, and 2 hours after preparation, and bioassays were conducted to determine the activity of aldesleukin in the combinations. Lorazepam was the only drug visually incompatible with aldesleukin. All the secondary drugs were spectrophotometrically compatible with aldesleukin. However, the bioassays showed that the following drugs reduced the activity of aldesleukin: ganciclovir sodium, lorazepam, pentamidine isethionate, prochlorperazine edisylate, and promethazine hydrochloride. Thus, aldesleukin became less biologically active when combined with four drugs for which visual examination suggested compatibility and when combined with five drugs for which spectrophotometry indicated compatibility. Aldesleukin 33,800 IU/mL in 5% dextrose injection lost significant biological activity in the presence of prochlorperazine edisylate, promethazine hydrochloride, lorazepam, ganciclovir sodium, and pentamidine isethionate during simulated Y-site administration. Visual assessment and spectrophotometry may not be valid methods for assessing possible changes in the biological activity of aldesleukin when combined with other agents.     

Ligands with affinity to specific sequences of DNA base pairs. X. Synthesis and binding of netropsin analogs, containing a chelating copper ion peptide, with DNA

An analogue of netropsin has been synthesized consisting of two N-propylpyrrolcarboxamide units linked covalently to a copper-chelating tripeptide Gly-Gly-L-His by means of two and three glycine residues. Binding to DNA and synthetic polynucleotides of netropsin analogue containing three glycine residues between Gly-Gly-L-His tripeptide and the N-end of netropsin analogue (His-Nt) has been studied. It is shown that this netropsin analogue chelates a copper ion with 1:1 stoichiometry, similar to a free Gly-Gly-L-His peptide. It is found that this netropsin analogue occupies 3 to 4 base pairs upon binding to poly(dA).poly(dT) and poly[d(AT)].poly[d(AT)] polymers, irrespective of whether it binds in Cu(2+)-ligated or unligated forms. Binding constants and binding site sizes have been calculated for netropsin analogue complexes with DNA, poly(dA).poly(dT) and poly[d(AT)].poly[d(AT)] polymers at the [Cu2+]/[His-Nt] ratio equal to 0 and 1.0. In the three-component system including His-Nt and Cu(2+)-His-Nt, cooperative effects are recognized which can be explained by heterodimer generation on interaction of His-Nt and Cu(2+)-His-Nt at adjacent binding sites.     

Pharmacodynamic modeling of the electroencephalographic effects of flumazenil in healthy volunteers sedated with midazolam

The purpose of this study was to model pharmacodynamically the reversal of midazolam sedation with flumazenil. Ten human volunteers underwent four different sessions. In session 1, individual midazolam pharmacokinetics and electroencephalographic pharmacodynamics were determined. In sessions 2 and 3, a computer-controlled infusion of midazolam with individual volunteer pharmacokinetic data was administered, targeting a plasma concentration corresponding to a light or deep level of sedation (20% or 80% of the maximal midazolam electroencephalographic effect) for a period of 210 minutes. After obtaining a stable electroencephalographic effect and constant midazolam plasma concentrations, a zero-order infusion of flumazenil was started until complete reversal of midazolam electroencephalographic effect was obtained. The flumazenil infusion was then stopped and the volunteer was allowed to resedate because of the constant midazolam drug effect. The electroencephalographic response was measured during a 180-minute period and analyzed by aperiodic analysis and fast-Fourier transforms. In session 4, a midazolam plasma concentration corresponding to a deep level of sedation was targeted for 210 minutes to examine for the possible development of acute tolerance. No flumazenil was given in session 4. For a light sedation level, with a mean midazolam plasma concentration of 160 +/- 64 ng/ml, the mean half-life of the equilibration rate constant of flumazenil reversal is 5.0 +/- 2.5 minutes, and the mean effect site concentration causing 50% of Emax is 13.7 +/- 5.8 ng/ml. For a deep level of sedation, with a mean midazolam plasma concentration of 551 +/- 196 ng/ml, the mean half-life of the equilibration rate constant is 3.9 +/- 1.5 minutes, and the mean effect site concentration causing 50% of Emax is 20.6 +/- 6.8 ng/ml. This study provides an estimate of the magnitude of the blood/central nervous system equilibration delay for flumazenil antagonism of midazolam sedation and further defines the usefulness of the electroencephalogram as a measure of midazolam pharmacodynamic effect.     

Effect of stress triaxiality levels in crack tip regions on the characteristics of void growth and fracture criteria

The behaviour of void growth in the crack tip regions of four specimen geometries with different stress triaxiality levels have been investigated by the FEM method and experimental observations in plane strain and plane stress cases respectively. It was found that the shape change of growing voids, the configurations of a blunting crack tip and the sizes of decreasing ligament between the void and the crack tip are strongly dependent upon the stress triaxiality levels. Under the condition of plane stress, the stress triaxiality on the ligaments of cracks are nearly the same for different specimen geometries, also the void growth, crack tip blunting asnd decreasing of ligament size are identical for various specimens with increasing load levels, which lead to the conclusion that the J_i-value is independent of specimen geometries. However, in the plain strain case, different void growth, crack tip blunting and decreasing in ligament size for various stress triaxiality levels directly caused the J_i-value to be dependent on the specimen geometries. It was found that when the void is linked to the blunting crack tip by the extrapolation to the zero ligament from FEM calculations, the J_i values, measured experimentally, are underestimated slightly.     

Highly active lanthanum doped nickel anode for solid oxide fuel cells directly fuelled with methane

Lanthanum doped nickel and YSZ composite anode (LaNi–YSZ) exhibited a greatly reduced polarization resistance and high performance for electrochemical oxidation of hydrogen and methane, which resulted from a fine anode structure with a high dispersion of nickel catalyst and a high catalytic activity towards methane.     

F150交换机告警关联规则的研究

为了提高电信网络运营效率，降低维护成本，电信运营企业在网络告警管理系统中需要引入数据挖掘技术。本文主要研究利用数据挖掘技术来进行故障的管理，即对告警进行关联性分析，详细分析了告警序列数据的关联规则挖掘算法，并在南昌本地网F150交换机的告警数据库中予以实现，同时对实际挖掘结果进行分析和整理，推导出一些实用的关联规则。     

Hyperdynamic circulation of cirrhotic rats: role of substance P and its relationship to nitric oxide

BACKGROUND: It has been suggested that excessive formation of nitric oxide (NO) is responsible for the hyperdynamic circulation observed in portal hypertension. Substance P is a neuropeptide partly cleared by the liver and causes vasodilatation through the activation of the endothelial NO pathway. However, there are no previously published data concerning the plasma level of substance P in cirrhotic rats and its relationship to NO. METHODS: Plasma concentrations of substance P and nitrate/nitrite (an index of NO production) were determined in control rats and cirrhotic rats with or without ascites using an enzyme-linked immununosorbent assay and a colorimetric assay, respectively. In addition, systemic and portal hemodynamics were evaluated by a thermodilution technique and catheterization. RESULTS: Cirrhotic rats with and without ascites had a lower systemic vascular resistance (2.6 +/- 0.2 and 3.9 +/- 0.4 mmHg ml(-1) x min x 100 g body weight, respectively) and higher portal pressure (14.6 +/- 0.6 and 11.3 +/- 1.8 mmHg) than control rats (6.5 +/- 0.3 mmHg x ml(-1) x min x 100 g BW and 6.8 +/- 0.2 mmHg, respectively, P < 0.05), and cirrhotic rats with ascites had the lowest systemic vascular resistance. Plasma levels of nitrate/nitrite progressively increased in relation to the severity of liver dysfunction (control rats, 2.7 +/- 0.5 nmol/ml; cirrhotic rats without ascites, 5.6 +/- 1.3 nmol/ml; cirrhotic rats with ascites, 8.3 +/- 2.2 nmol/ml; P < 0.05). Cirrhotic rats with ascites displayed higher plasma values of substance P (57.7 +/- 5.9 pg/ml) than cirrhotic rats without ascites (37.9 +/- 3.1 pg/ml, P < 0.05) and control rats (30.1 +/- 1.0 pg/ml, P < 0.05). There was no significant difference in plasma substance P values between control rats and cirrhotic rats without ascites (P > 0.05). No correlation was found between plasma levels of substance P and nitrate/nitrite (r = 0.318, P > 0.05). CONCLUSIONS: Excessive formation of NO may be responsible, at least partly, for the hemodynamic derangements in cirrhosis. Although substance P may not participate in the initiation of a hyperdynamic circulation in cirrhosis, it may contribute to the maintenance of the hyperdynamic circulation observed in cirrhotic rats with ascites.     

Identification of extractable growth factors from small intestinal submucosa

When implanted as a biomaterial for tissue replacement, selected submucosal layers of porcine small intestine induce site-specific tissue remodeling. Small intestinal submucosa (SIS), as isolated, is primarily an acellular extracellular matrix material. In an attempt to discover the components of small intestinal submucosa which are able to induce this tissue remodeling, the material was extracted and extracts were tested for the ability to stimulate Swiss 3T3 fibroblasts to synthesize DNA and proliferate. Each of the four different extracts of small intestinal submucosa had measurable cell-stimulating activity when analyzed in both a whole cell proliferation assay (alamarBlue dye reduction) and a DNA synthesis assay ([3H]-thymidine incorporation). Proteins extracted from SIS with 2 M urea induced activity profiles in the two assays which were very similar to the activity profiles of basic fibroblast growth factor (FGF-2) in the assays. As well, the changes in cell morphology in response to the extracted proteins mimicked the changes induced by FGF-2. Neutralization experiments with specific antibodies to this growth factor confirmed the presence of FGF-2 and indicated that it was responsible for 60% of the fibroblast-stimulating activity of the urea extract of small intestinal submucosa. Western blot analysis with a monoclonal antibody specific for FGF-2 detected a reactive doublet at approximately 19 kDa and further confirmed the presence of FGF-2. Cell stimulating activity of proteins extracted from SIS with 4 M guanidine was neutralized by an antibody specific for transforming growth factor beta (TGF beta). Changes in the morphology of the fibroblasts exposed to this extract were nearly identical to changes induced by TGF beta. Although no reactive protein band was detected at 25 kDa in nonreduced western blot analysis, several bands were reactive at higher molecular weight. The identity of this TGF beta-related component of small intestinal submucosa is unknown. Identification of FGF-2 and TGF beta-related activities in SIS, two growth factors known to significantly affect critical processes of tissue development and differentiation, provides the opportunity to further elucidate the mechanisms by which this extracellular matrix biomaterial modulates wound healing and tissue remodeling.