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181.
The purpose of the present work was to compare the behavior of some drug/carrageenan complexes having different solubility in water, in a controlled release formulation. Diltiazem HCl, bupropion HCl, metoprolol tartrate, and tramadol HCl were used as model drugs. The complexes were characterized by means of solubility measurements, release test at constant surface area, and water uptake measurements, and the results were related to their performance in controlled release formulations. For the more soluble complexes (involving metoprolol and tramadol) the occurrence of gelation after hydration was observed, while diltiazem complex apparently did not gellify; bupropion behavior was intermediate. A correspondence was found between the observed differences in complex solubility and hydration-gelation behavior and the drug release profiles. For all the drugs considered, the release was completed in about 10 to 12 hours, but different kinetics were observed depending on the solubility of the complexes. All the considered complexes seem suitable for controlled release purposes, although the data obtained show the relevance of the complex solubility to drug release profiles. 相似文献
182.
Gioacchino Micheli Anna Rosa Ciofi Luzzatto Maria Teresa Carrì Adriana de Capoa Franca Pelliccia 《Chromosoma》1993,102(7):478-483
The looped organization of the eukaryotic genome mediated by a skeletal framework of non-histone proteins is conserved throughout the cell cycle. The radial loop/scaffold model envisages that the higher order architecture of metaphase chromosomes relies on an axial structure around which looped DNA domains are radially arranged through stable attachment sites. In this light we investigated the relationship between the looped organization and overall morphology of chromosomes. In developing Xenopus laevis embryos at gastrulation, the bulk of the loops associated with histone-depleted nuclei exhibit a significant size increase, as visualized by fluorescence microscopy of the fully extended DNA halo surrounding high salt treated, ethidium bromide stained nuclei. This implies a reduction in the number of looped domains anchored to the supporting nucleoskeletal structure. The cytological analysis of metaphase plates from acetic acid fixed whole embryos, carried out in the absence of drugs inducing chromosome condensation, reveals a progressive thickening and shortening of metaphase chromosomes during development. We interpret these findings as a strong indication that the size and number of DNA loops influence the thickness and length of the chromosomes, respectively. The quantitative analysis of chromosome length distributions at different developmental stages suggests that the shortening is timed differently in different embryonic cells. 相似文献
183.
The transmembrane electropotential of microsomal vesicles from pea internode segments, monitored by equilibrium distribution of the permeant anion SCN?, is strongly hyperpolarized when ATP is present in the incubation medium.The stimulation of SCN? uptake by ATP is rather specific with respect to the other nucleoside di- and triphosphates tested: ADP, GTP, CTP and UTP. ATP-stimulated SCN? uptake is strongly inhibited by ATPase inhibitors such as and and by 2.5% toluene/ethanol (1 : 4, v/v), the latter being a treatment which makes the vesicles permeable. On the contrary, oligomycin is almost ineffective in influencing ATP-induced SCN? uptake. The proton conductor carbonyl cyanide strongly inhibits ATP-stimulated SCN? uptake. The effect of ATP on SCN? uptake depends on the pH of the medium, the maximum being reached at about pH 7.0.These data support the view that microsomal fractions from pea internodes contain membrane vesicles endowed with a membrane-bound ATPase coupling ATP hydrolysis to electrogenic transport of ions, probably H+. 相似文献
184.
Giulia Acerbis Loredana Cleris Monica Rodolfo Giorgio Parmiani Franca Formelli 《Cancer immunology, immunotherapy : CII》1992,34(6):383-388
Summary The efficacy of the association of recombinant interleukin-2 (rIL-2) with chemotherapy has been investigated on an experimental model representative of clinical tumours, i.e. on post-surgical spontaneous metastases of a non-immunogenic tumour. We used the M5076 ovarian reticulum cell sarcoma, which metastatizes to the liver after intra-footpad implantation. Such a tumour appeared to be non-immunogenic by a variety of commonly used in vivo assays. Four clinically widely employed drugs, i.e. doxorubicin,cis-diamminedichloroplatinum II, cyclophosphamide and 1,3-bis-(2-chloroethyl)-1-nitrosurea (BCNU), were tested and BCNU proved to be the most effective one when administered as single injection at the maximum tolerated dose (33 mg/kg i.p.) 1 day after tumour excision. When moderate doses of rIL-2 (6 × 105 IU in three injections per day for 5 days) were administered at three different intervals after BCNU, namely before the nadir of white blood cells (1 day after BCNU), at the nadir (3 days after BCNU) or at recovery (6 days after BCNU), no increase in BCNU antitumour activity was observed. The same results were obtained by administering rIL-2 for 5 days before BCNU. Higher doses of rIL-2 (1.2 × 106 IU in three injections per day for 5 days), which were always well tolerated in sham-excised non-tumour-bearing mice, proved lethal in two out of four experiments in tumour-bearing animals. In the two experiments in which no lethality was observed, the administration of high doses of rIL-2 1 or 6 days after BCNU significantly increased the antitumour activity of BCNU alone. rIL-2 alone was not active even when administered at high doses. These results indicate that high but not moderate doses of rIL-2 may increase the activity of BCNU against a non-immunogenic tumour. Moreover, they suggest that rIL-2 tolerability is reduced in tumour-bearing mice. 相似文献
185.
Edon Melloni Franca Salamino Bianca Sparatore Mauro Michetti Sandro Pontremoli 《Archives of biochemistry and biophysics》1982,216(2):495-502
Human erythrocytes are shown to contain soluble proteinase(s) that convert excess β-hemoglobin introduced by in vitro entrapment to modified forms that are bound to the erythrocyte membrane. The bound modified hemoglobin chains are degraded in the membrane to yield acid soluble products. Native hemoglobin chains are not bound to the membrane and are not degraded. The cooperative degradation of excess β-hemoglobin chains by soluble and membrane-bound enzymes occurs at neutral pH and does not require energy. The results provide a role for the membrane-bound acid proteinases. 相似文献
186.
The human CD38 gene: polymorphism, CpG island, and linkage to the CD157 (BST-1) gene 总被引:7,自引:0,他引:7
CD38 is a leukocyte activation antigen and ectoenzyme [NAD(P)+ glycohydrolase; EC 3.2.2.6] involved in numerous immune functions. The human CD38 gene is complex [eight exons, >80 kilobases (kb) long] located on Chromosome 4p15, and part of the eukaryotic NAD+ glycohydrolase/ADP-ribosyl cyclase gene family. Because of the increasing relevance of the CD38 molecule in the host immune
response to infectious, tumoral, and metabolic diseases, we investigated the genetic variability and linkage of the human
CD38 locus. We report that (1) the restriction endonuclease Pvu II identifies a bi-allelic polymorphism here defined as formed by the alleles CD38
*
A (12 kb) and CD38
*
B (9/2.5 kb); (2) their frequency in the healthy Italian Caucasian population is 14% and 86%, respectively; (3) the polymorphic
Pvu II site is located at the 5′ end of the first intron of the CD38 gene; (4) in conjunction with the polymorphic site, we identified a 900 base pair CpG island associated with the CD38 gene, with two potential Sp1 binding sites; (5) the CpG island may play a role in the regulation of CD38 expression and is hypomethylated in various cell lines; (6) by pulsed-field gel electrophoresis we show that CD38 and its paralogue, the bone-marrow stromal cell antigen BST-1 (CD157), map to the same 800 kb Avi II fragment, indicating that the two human ecto-NADase genes are closely linked.
Received: 16 December 1998 / Revised: 26 January 1999 相似文献
187.
Oligodendrocytes, the myelinating cells of the central nervous system, are terminally differentiated cells that originate through asynchronous waves of proliferation and differentiation of precursors present at birth. Withdrawal from cell cycle and onset of differentiation are tightly linked and depend on an intrinsic program modulated by the action of growth factors. p27 plays a central and obligatory role in the initiation of oligodendrocyte differentiation and cessation of proliferation. In this paper, we have characterized the role of modulation of cdk2 and cdk5 kinase activity during the process of oligodendrocyte precursor differentiation. As rat primary oligodendrocytes differentiate in culture there is a fall in cdk2 activity and a rise in cdk5 activity as well as an increase in the cdk inhibitor, p27 protein. The decline in cdk2 activity is not accompanied by a drop in cdk2 protein level, suggesting that it results from inhibition of cdk2 activation rather than decreased protein expression. Taken together, these data suggest that oligodendrocytes may withdraw from the cell cycle at G1-S transition through inactivation of cdk2 activity, possibly initiated by increasing amount of p27, and that cdk5 may have a role until now unrecognized in the differentiation of oligodendrocytes. J. Cell. Biochem. 68:128–137, 1998. © 1998 Wiley-Liss, Inc. 相似文献
188.
Vittorio Romano Lucia Paciello Franca Romano Elisabetta de Alteriis Luca Brambilla Palma Parascandola 《Process Biochemistry》2009,44(5):527-533
A cultural system, aimed at the production of human interleukin-1β (IL-1β) with cells of a non-conventional yeast transformed for interleukin expression, Zygosaccharomyces bailii [pZ3KlIL-1β], was realized. Interleukin production was accomplished in a reactor operating in fed-batch mode to avoid sugar overflow metabolism, limitations with respect to oxygen transfer, and achieve high cell density. Batch operation mode was employed only to characterise the producer strain and experimentally estimate kinetic parameters. In parallel with strain characterisation, a mathematical model was developed. The comparison between simulations and experimental data allowed to evidence the importance of physiological state of inoculum, being only a fermentative one suitable to sustain a given exponential growth. The respiratory capacity of Z. bailii [pZ3KlIL-1β], resulted to be affected by stirring. The theoretical and experimental approach allowed the bioprocess optimisation. 相似文献
189.
Paola?Caroppi Federica?Sinibaldi Elisa?Santoni Barry?D.?Howes Laura?Fiorucci Tommaso?Ferri Franca?Ascoli Giulietta?Smulevich Roberto?SantucciEmail author 《Journal of biological inorganic chemistry》2004,9(8):997-1006
The structural and redox properties of a non-covalent complex reconstituted upon mixing two non-contiguous fragments of horse cytochrome c, the residues 1–38 heme-containing N-fragment with the residues 57–104 C-fragment, have been investigated. With respect to native cyt c, the complex lacks a segment of 18 residues, corresponding, in the native protein, to an omega ()-loop region. The fragment complex shows compact structure, native-like -helix content but a less rigid atomic packing and reduced stability with respect to the native protein. Structural heterogeneity is observed at pH 7.0, involving formation of an axially misligated low-spin species and consequent partial displacement of Met80 from the sixth coordination position of the heme-iron. Spectroscopic data suggest that a lysine (located in the Met80-containing loop, namely Lys72, Lys73, or Lys79) replaces the methionine residue. The residues 1–38/57–104 fragment complex shows an unusual biphasic alkaline titration characterized by a low (pKa1=6.72) and a high pKa-associated state transition (pKa2=8.56); this behavior differs from that of native cyt c, which shows a monophasic alkaline transition (pKa=8.9). The data indicate that the 40s -loop plays an important role in the stability of cyt c and in ensuring a correct alkaline conformational transition of the protein. 相似文献
190.
NAAG peptidase inhibition reduces locomotor activity and some stereotypes in the PCP model of schizophrenia via group II mGluR 总被引:2,自引:0,他引:2
Olszewski RT Bukhari N Zhou J Kozikowski AP Wroblewski JT Shamimi-Noori S Wroblewska B Bzdega T Vicini S Barton FB Neale JH 《Journal of neurochemistry》2004,89(4):876-885
Phencyclidine (PCP) administration elicits positive and negative symptoms that resemble those of schizophrenia and is widely accepted as a model for the study of this human disorder. Group II metabotropic glutamate receptor (mGluR) agonists have been reported to reduce the behavioral and neurochemical effects of PCP. The peptide neurotransmitter, N-acetylaspartylglutamate (NAAG), is a selective group II agonist. We synthesized and characterized a urea-based NAAG analogue, ZJ43. This novel compound is a potent inhibitor of enzymes, glutamate carboxypeptidase II (K(i) = 0.8 nM) and III (K(i) = 23 nM) that deactivate NAAG following synaptic release. ZJ43 (100 microM) does not directly interact with NMDA receptors or metabotropic glutamate receptors. Administration of ZJ43 significantly reduced PCP-induced motor activation, falling while walking, stereotypic circling behavior, and head movements. To test the hypothesis that this effect of ZJ43 was mediated by increasing the activation of mGluR3 via increased levels of extracellular NAAG, the group II mGluR selective antagonist LY341495 was co-administered with ZJ43 prior to PCP treatment. This antagonist completely reversed the effects of ZJ43. Additionally, LY341495 alone increased PCP-induced motor activity and head movements suggesting that normal levels of NAAG act to moderate the effect of PCP on motor activation via a group II mGluR. These data support the view that NAAG peptidase inhibitors may represent a new therapeutic approach to some of the components of schizophrenia that are modeled by PCP. 相似文献