A new model describing the swelling and drug release kinetics from hydroxypropyl methylcellulose tablets

BACKGROUND: Catecholamines hasten cardiac relaxation through beta-adrenergic receptors, presumably by phosphorylation of several proteins, but it is unknown which receptor subtypes are involved in human ventricle. We assessed the role of beta1- and beta2-adrenergic receptors in phosphorylating proteins implicated in ventricular relaxation. METHODS AND RESULTS: Right ventricular trabeculae, obtained from freshly explanted hearts of patients with dilated cardiomyopathy (n=5) or ischemic cardiomyopathy (n=5), were paced at 60 bpm. After measurement of the contractile and relaxant effects of epinephrine (10 micromol/L) or zinterol (10 micromol/L), mediated through beta2-adrenergic receptors, and of norepinephrine (10 micromol/L), mediated through beta1-adrenergic receptors, tissues were freeze clamped. We assessed phosphorylation of phospholamban, troponin I, and C-protein, as well as specific phosphorylation of phospholamban at serine 16 and threonine 17. Data did not differ between the 2 disease groups and were therefore pooled. Epinephrine, zinterol, and norepinephrine increased contractile force to approximately the same extent, hastened the onset of relaxation by 15+/-3%, 5+/-2%, and 20+/-3%, respectively, and reduced the time to half-relaxation by 26+/-3%, 21+/-3%, and 37+/-3%. These effects of epinephrine, zinterol, and norepinephrine were associated with phosphorylation (pmol phosphate/mg protein) of phospholamban 14+/-3, 12+/-4, and 12+/-3; troponin I 40+/-7, 33+/-7, and 31+/-6; and C-protein 7.2+/-1.9, 9.3+/-1.4, and 7.5+/-2.0. Phosphorylation of phospholamban occurred at both Ser16 and Thr17 residues through both beta1- and beta2-adrenergic receptors. CONCLUSIONS: Norepinephrine and epinephrine hasten human ventricular relaxation and promote phosphorylation of implicated proteins through both beta1- and beta2-adrenergic receptors, thereby potentially improving diastolic function.     

Sustained-release dosage form of phenylpropanolamine hydrochloride. Part II: Formulation and in vitro release kinetics from tableted microcapsules

This work was planned to prepare sustained-action preparations of phenylpropanolamine hydrochloride by microencapsulation and by tableted microcapsules. Dissolution from both suspended microcapsules and the tablets was studied using the USP XXII basket method in simulated gastric and intestinal fluid without enzyme. The results were applied to zero-order, first-order, Hixson Crowell, RRSBW, Q/square root of t, (Bt)a and Higuchi kinetic models. Dissolution of PPA.HCl was found to be governed by the core:wall ratio, drug particle size, media pH and type of disintegrating agent. Dissolution kinetics were studied and evaluated.     

Preparation of fine copper powders from organic media by reaction with hydrogen under pressure: Part II. The kinetics of particle nucleation,growth, and dispersion

The kinetics of very tine copper powder (1 to 2 μm) production by hydrogen reduction of solvent extracted copper chelates have been determined. The Avrami-Erafeer model for nucleation growth processes has been found to best describe the precipitation kinetics. The model parameters were correlated with reasonable success to the morphology of the copper powder. The chemically controlled particle formation process was found to exhibit 30 to 58 kJ/mol activation energy depending on the temperature range and a complex dependency (from first order to fractional/zero order) on hydrogen pressure. A steric stabilization model has been advanced to interpret the cooperative action of decanol and Versatic 10 in stabilizing the very fine copper powder dispersion.     

Preparation and evaluation of sodium diclofenac controlled-release tablets. II. Dibasic calcium phosphate as a retardant in mixtures for direct compression

Malignant melanoma of the skin has become a real problem due to the increasing number of cases. No other tumor is induced by long term UV-radiation of the skin. Excision of the primary tumor is the treatment of choice in this disease. Before excision of the tumor lymphoscintigraphy is the first choice in diagnosis to demonstrate the draining lymph vessels and lymph node groups of an malignant melanoma for later operation. This work current the status quo of lymphoscintigraphy in malignant melanoma of the trunk.     

Deducing polymeric structure from aqueous molecular dynamics simulations of oligosaccharides: predictions from simulations of hyaluronan tetrasaccharides compared with hydrodynamic and X-ray fibre diffraction data

Molecular dynamics simulations of the two hyaluronan tetrasaccharides in water predict that over a period of 500 ps, their central linkages populate a single primary minima. Over the same period the peripheral linkages explore this minima, but also a secondary minima. Structures constructed using the primary minima were found to be extended left-handed helices of axial rise per disaccharide (h) 0.8 to 1.0 nm and 2.8 to 4.5 disaccharides per turn (n), in good agreement with n=3 and n=4 helices found by X-ray fibre diffraction studies. We have used the predicted average conformation from molecular dynamics to calculate the translational diffusion coefficients of the oligosaccharide series up to decasaccharide, and compared these with experimental measurements obtained using the method of capillary dispersion. Our calculated values are found to be in good agreement with experiment beyond the size of a tetrasaccharide. A partial digest of hyaluronan in the molecular mass range 10 to 100 kDa was fractionated by gel chromatography. Molecular weights were determined by in-line laser light-scattering measurements, and the translational diffusion coefficients of selected fractions were determined by dynamic laser light-scattering. A similar experiment was performed on hyaluronan with a molecular mass greater than 1MDa. The data suggest a change from rod-like to stiff coil behaviour beyond a molecular weight of 10 kDa. We have also examined the conformations available using the secondary minima, found at the peripheral linkages. In contrast to the extended structures previously described we have found left and right-handed helices with high values of n (5-10) and low values of h. Although there is no experimental evidence for these structures, they are of interest as, over short stretches, they would introduce folds, loops, and turns into the hyaluronan molecule. Such shapes may play an important role in the hydrodynamics of hyaluronan and its interaction with lipids and proteins.     

Extraction equilibrium and extraction kinetics of nickel from aqueous ammonium nitrate solution with versatic 10 in n-hexane

The mechanism of extraction of nickel from an aqueous ammonia-ammonium nitrate mixture by an n-hexane solution of Versatic 10 was investigated from the viewpoint of extraction equilibrium and extraction kinetics. From the equilibrium study, it was found that nickel is extracted according to the following two extraction reactions which are in accordance with the loading ratio of nickel to Versatic 10:

$\text{Ni}{}^{\mathrm{2+}}\text{+ 3 H}{}_2\text{R}{}_{\mathrm{2org}}\text{?NiR}{}_2\text{·4 HR}{}_{\mathrm{org}}\text{+2 H}{}^{\mathrm{+}}{}_{\mathrm{aq}}$

in the range of lower loading ratio, and

$\text{2 Ni}{}^{\mathrm{2+}}{}_{\mathrm{aq}}\text{+ 4 H}{}_2\text{R}{}_{\mathrm{2org}}\text{?(NiR}{}_2\text{·2 HR)}{}_{\mathrm{2org}}\text{+4 H}{}^{\mathrm{+}}{}_{\mathrm{aq}}$

in the range of higher loading ratio. The equilibrium constants for each reaction were also determined. From the study of extraction kinetics, the extraction rate was found to be proportional to the total concentrations of nickel and Versatic 10 and inversely proportional to that of hydrogen ion. A reaction mechanism is proposed in order to give a reasonable explanation for the observed concentration dependence of each of the reactant species.     

Peroxynitrite reaction with carbon dioxide/bicarbonate: kinetics and influence on peroxynitrite-mediated oxidations

A method of stratifying the data according to the patterns of missing observations, summarizing each subject's repeated measurements by a summary measure and then comparing the treatment groups with the help of a distribution-free test based on the summary measure, is used here to compare the efficacy of tacrine dose regimens with that of placebo in a recent trial in Alzheimer's disease patients. The usefulness of the method of meta-analysis for comparing the treatment groups, in the presence of missing data, is also investigated.     

Executive turnover: The influence of dispersion and other pay system characteristics.

Using tournament theory as a guiding theoretical framework, in this study, we assess the organizational implications of pay dispersion and other pay system characteristics on the likelihood of turnover among individual executives in organizational teams. Specifically, we estimate the effect of these pay system characteristics on executive turnover decisions. We use a multi-industry, multilevel data set composed of executives in publicly held firms to assess the effects of pay dispersion at the individual level. Consistent with previous findings, we find that pay dispersion is associated with an increased likelihood of executive turnover. In addition, we find that other pay characteristics also affect turnover, both directly and through a moderating effect on pay dispersion. Turnover is more likely when executives receive lower portions of overall top management team compensation and when they have more pay at risk. These conditions also moderate the relationship between pay dispersion and individual turnover decisions, as does receiving lower compensation relative to the market. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Effects of drug solubility, drug loading, and polymer molecular weight on drug release from Polyox tablets

BACKGROUND: This study augments a randomized controlled trial to analyze the cost-effectiveness of 2 standardized treatments for major depression relative to each other and to the "usual care" provided by primary care physicians. METHODS: A randomized controlled trial was conducted in which primary care patients meeting DSM-III-R criteria for current major depression were assigned to pharmacotherapy (where nortriptyline hydrochloride was given) or interpersonal psychotherapy provided in a standardized framework or a primary physician's usual care. Two outcome measures, depression-free days and quality-adjusted days, were developed using information on depressive symptoms over time. The costs of care were calculated. Cost-effectiveness ratios comparing the incremental outcomes with the incremental costs for the different treatments were estimated. Sensitivity analyses were performed. RESULTS: In terms of both economic costs and quality-of-life outcomes, patients assigned to the pharmacotherapy group did slightly better than those assigned to interpersonal psychotherapy. Both standardized therapies provided better outcomes than primary physician's usual care, but each consumed more resources. No meaningful cost-offsets were found. The incremental direct cost per additional depression-free day for pharmacotherapy relative to usual care ranges from $12.66 to $16.87 which translates to direct cost per quality-adjusted year gained from $11270 to $19510. CONCLUSIONS: Standardized treatments for depression lead to better outcomes than usual care but also lead to higher costs. However, the estimates of the cost per quality-of-life year gained for standardized pharmacotherapy are comparable with those found for other treatments provided in routine practice.     

奥氏体不锈钢在含锌PWR一回路水中的均匀腐蚀行为

在模拟压水堆一回路水化学环境中,对主管道316L不锈钢和Stellite 6钴基合金分别开展了0,10,40 μg·L^–1三种Zn质量浓度的均匀腐蚀试验. 试验结束后,采用失重法计算两种材料的腐蚀速率和腐蚀产物释放速率,采用扫描电子显微镜（SEM）、透射电镜能谱仪（TEM-EDS）以及高分辨和傅里叶转变分析氧化膜表面形貌、截面形貌、厚度、元素分布以及双层氧化膜相结构. 结果表明,对于316L不锈钢,1000 h内10 μg·L^–1 Zn的注入对腐蚀速率和释放速率影响不显著,增加Zn质量浓度至40 μg·L^–1后,316L不锈钢的腐蚀速率、腐蚀产物释放速率和氧化膜厚度显著降低,其中氧化膜厚度由250 nm降低至95 nm. 对于具有双相结构的Stellite 6钴基合金,γ-Co基体和碳化物间存在电偶腐蚀效应,γ-Co基体和相界腐蚀更显著. 进一步延长腐蚀时间至3000 h,发现10 μg·L^–1 Zn注入可以显著降低其腐蚀速率和腐蚀产物释放速率,当Zn质量浓度增加至40 μg·L^–1时,钴基合金的腐蚀速率、腐蚀产物释放速和氧化膜厚度进一步降低. 微观分析表明,注锌对两种合金腐蚀抑制机理相似,注入的Zn离子会在金属表面形成含Zn的尖晶石结构,显著提高外层氧化膜的致密性,阻碍金属离子向外扩散及氧离子向内扩散,促进内层氧化膜/基体界面处保护性Cr₂O₃的形成,进而显著降低316L不锈钢和Stellite 6钴基合金的腐蚀速率、腐蚀产物释放速率和氧化膜厚度.

     

Stress corrosion cracking of zirconium cladding tubes: II. Mechanisms and kinetics

The mechanisms and kinetics of corrosion fracture of thin-wall cladding tubes of zirconium alloys in a methanol-iodine medium are determined by a direct comparison of the acoustic emission parameters with the characteristics of accumulated corrosion defects in a material during stress corrosion cracking tests. The main types of corrosion defects (nucleation, development, interaction) are revealed and quantitatively described. A general sequence of nucleation and development of corrosion defects is established for all types of tubes.     

Quantitative evaluation of selective thrombolysis techniques: influence of catheter characteristics and delivery parameters

The outcome of H. pylori infectins depends on proliferation of various host cells, including lymphocytes, monocytes and epithelial cells. In this study we showed that a recombinant fusion protein carrying an immunodominant region of H. pylori CagA antigen affected the proliferation of human cells. The rCagA inhibited PHA-driven T cell proliferation but enhanced the growth of epithelial HeLa cells, especially in the presence of granulocyte macrophage colony stimulating factor (GM-CSF). When THP-1 monocytes and Kato-3 epithelial cells from metastasis of gastric carcinoma were stimulated with GM-CSF, they were also susceptible to the inhibitory effect of rCagA. These results confirmed our earlier suggestion on the inhibition of T cell function by H. pylori CagA protein. However, antiproliferative activity of CagA antigen appears to be not restricted to T lymphocytes but modulatory effect of this protein seems to depend on the cell type.     

NMDA-receptor contribution to spinal nociceptive reflexes: influence of stimulus parameters and of preparatory surgery

The contribution of NMDA receptors to nociceptive reflexes has been assessed both in awake rats and in electrophysiological tests on alpha-chloralose anaesthetized spinalized rats prepared with different degrees of surgery. Single motor unit activity was recorded in response to alternating noxious mechanical and electrical stimuli applied to one hindpaw, and the results compared with paw pressure withdrawal reflexes in awake rats. There was little contribution by NMDA receptors to nociceptive paw pinch responses either in awake rats or in rats prepared with minimal surgery, but following extensive lumbar surgery the contribution increased significantly to a level similar to that seen in the wind-up component of responses elicited by electrical stimulation. Surgery therefore has effects several segments from the sensory input that it generates. It enhances the NMDA receptor contribution in responses to some but not all types of afferent input.     

Structure and properties of rapidly solidified dispersion strengthened titanium alloys: Part II. tensile and creep properties

The effects of incoherent dispersoids on tensile and creep properties were determined in rapidly solidified Ti-Er and Ti-Nd alloys. Uniform distributions of. fine incoherent dispersoids in Ti matrix were produced by rapid solidification at cooling rates > 10³ °C per second and subsequent annealing at 700 to 800°C of Ti-1.0Er, Ti-2.0Er, Ti-1.5Nd, and Ti-3.0Nd alloys. The rapidly solidified particulates consolidated by vacuum hot pressing were isothermally forged, rolled, and annealed to produce fully recrystallized microstructures. The incoherent dispersoids in Ti-Er and Ti-Nd alloys increase by 40 to 110 pct the yield strength and ultimate tensile strength of Ti with no significant loss in ductility. The strength increments were analyzed in terms of the superposition of dispersion-, solid solution-, and fine grain-strengthening. Dispersion strengthening is offset to some extent by the reduction in interstitial oxygen solid solution strengthening caused by the scavenging of oxygen by Er and Nd. The dispersoids decrease the creep rates and increase the stress rupture lifetimes of Ti at 482 to 700 °C.     

The influence of metyrapone on the synthesis and release of prostaglandins from the pregnant rat uterus in vitro

1 Metyrapone (150 mg/kg, s.c. or i.p.) an inhibitor of corticosteroid biosynthesis, significantly reduced the release of prostaglandins of the F-type from isolated preparations of pregnant rat uteri in vitro, on day 22 - the expected day of delivery. 2 Metyrapone and indomethacin administered in vitro both inhibited the conversion of 14C-arachidonic acid to prostaglandin E2 by homogenates of day 22 pregnant rat uteri. Metyrapone was approximately 150 times less potent than indomethacin. Although indomethacin also inhibited prostaglandin F2alpha production, metyrapone stimulated synthesis of this prostaglandin. The differential inhibition of prostaglandin synthesis by metyrapone may reflect sensitivity of the inhibitor to changes in experimental conditions. 3 Inhibition of prostaglandin synthesis may explain the effects of metyrapone on parturition in the rat.     

Removal of Cd (II) and Pb (II) from aqueous environment using Moringa Oleifera seeds as biosorbent: A low cost and ecofriendly technique for water purification

Ever-growing list of chemical contaminants released into the environment through excessive industrialization on a large scale includes numerous chemical pollutants more prominently heavy metals. The discharge of heavy metals in aqueous system and their removal have been a challenging task for environmentalists for last one decade. Keeping these views in mind, the present study highlights the efficacy of shelled Moringa oleifera seeds (SMOS) in decontaminating Cd (II) and Pb (II) ions from aqueous environment both present as single metal and as binary metal solution. The extent of adsorption capacity for Cd (II) and Pb (II) on Moringa oleifera seeds for binary metal ions [76.59% and 81.10%] was found to be low as compared to single metal ions [85.10% and 96.10%]. Morphological changes observed in Scanning Electron Micrographs of native and treated SMOS indicates the existence of biosorption phenomenon. Fourier Transform Infrared Spectrometry of the exhausted seed biomass highlights amino acids-metal interaction responsible for sorption phenomenon. The sorption capacity of regenerated biomass remained almost constant after three cycle of sorption suggesting that the lifetime cycle was sufficient for continuous application.     

Angiotensin II stimulates cardiac myocyte hypertrophy via paracrine release of TGF-beta 1 and endothelin-1 from fibroblasts

We examined the effects of different cytokine combinations and culture conditions on the expansion and modulation of cell surface antigens of CD34+ derived dendritic cells (DCs), the most efficient antigen-presenting cells capable of stimulating resting T cells in the primary immune response. Cells with a dendritic morphology and expressing HLA-DR, CD1a, S100 and CD83 were maximally expanded under serum-free conditions with the addition of SCF, GM-CSF, TNF-alpha, TGF-beta and Flt-3 ligand (fold increase of CD1a+ cells = 102 +/- 32 after 2 weeks of culture). CD34+ cells were also grown under continuous flow conditions in an artificial capillary system: after 14d of culture, the expansion in the total cell number was lower than that of the static cultures (3.3 +/- 2 v 18.9 +/- 4) but the percentage of CD1a+/CD83+/ CD80+ cells was considerably higher, whereas the CD14+ cells were significantly reduced (8.9 +/- 2 v 26 +/- 13). In continuous perfusion cultures, low levels of DC precursors and of LTC-IC were still present up to day 14. The DCs generated under flow conditions stimulated the mixed leucocyte reaction (MLR) more than the cells grown in static cultures. By electron microscopy, cells grown in the continuous flow system showed an increased number of large cells with numerous dendritic processes and abundant multilamellar complexes. The cells expanded under these conditions were sorted on the basis of their light-scatter properties into two fractions: one containing a predominance of CD1a+/S100+/ CD8 3+/CD80+/CD14- 'large cells' with great internal complexity (mature DCs); the second including 'small cells' either CD33+/CD14+, CD33+/CD15+ or CD33+/CD13-/CD14. The DCs generated and selected with this method are therefore particularly well suited for immunotherapeutic protocols.     

The coprecipitation behavior of Co(II) and Ni(II) with Fe(III), Cr(III) and Al(III) from aqueous ammoniacal solutions

The coprecipitation of cobalt(II) and nickel(II) with iron(III), chromium(III) and aluminum(III) from ammoniacal solutions has been investigated. The coprecipitation behavior was found to be very sensitive to the solution pH and total ammonia concentration. Co(II) and Ni(II) can be precipitated from low ammonia concentration solutions but are readily redissolved at higher ammonia concentrations. The coprecipitate of divalent and trivalent species was found to contain very large amounts of the divalent metals (up to a mole ratio M M(II)/M(III) of 2.5) when aluminum was the trivalent species, whereas with iron(III) or chromium(III), the ratio was only 0.5.