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91.
The purpose of the present investigation was to increase the solubility and dissolution rate of rofecoxib by the preparation
of its solid dispersion with polyvinyl pyrrolidone K30 (PVP K30) using solvent evaporation method. Drug-polymer interactions
were investigated using differential scanning calorimetry (DSC), x-ray diffraction (XRD), and Fourier transform infrared spectroscopy
(FTIR). For the preparation of rofecoxib mouth dissolve tablets, its 1∶9 solid dispersion with PVP K30 was used with various
disintegrants and sublimable materials. In an attempt to construct a statistical model for the prediction of disintegration
time and percentage friability, a 32 randomized full and reduced factorial design was used to optimize the influence of the amounts of superdisintegrant and subliming
agent. The obtained results showed that dispersion of the drug in the polymer considerably enhanced the dissolution rate.
The drug-to-carrier ratio was the controlling factor for dissolution improvement. FTIR spectra revealed no chemical incompatibility
between the drug and PVP K30. As indicated from XRD and DSC data, rofecoxib was in the amorphous form, which explains the
better dissolution rate of the drug from its solid dispersions. Concerning the optimization study, the multiple regression
analysis revealed that an optimum concentration of camphor and a higher percentage of crospovidone are required for obtaining
rapidly disintegrating tablets. In conclusion, this investigation demonstrated the potential of experimental design in understanding
the effect of the formulation variables on the quality of mouth dissolve tablets containing solid dispersion of a hydrophobic
drug. 相似文献
92.
Meier C Carter LG Sainsbury S Mancini EJ Owens RJ Stuart DI Esnouf RM 《Journal of molecular biology》2008,381(5):1098-1105
Uridine monophosphate (UMP) kinase is a conserved enzyme that catalyzes the ATP-driven conversion of uridylate monophosphate into uridylate diphosphate, an essential metabolic step. In prokaryotes, the enzyme exists as a homohexamer that is regulated by various metabolites. Whereas the enzymatic mechanism of UMP kinase (UK) is well-characterized, the molecular basis of its regulation remains poorly understood. Here we report the crystal structure of UK from Bacillus anthracis (BA1797) in complex with ATP at 2.82 Å resolution. It reveals that the cofactor, in addition to binding in the active sites, also interacts with separate binding pockets located near the center of the hexameric structure. The existence of such an allosteric binding site had been predicted by biochemical studies, but it was not identified in previous crystal structures of prokaryotic UKs. We show that this putative allosteric pocket is conserved across different bacterial species, suggesting that it is a feature common to bacterial UKs, and we present a structural model for the allosteric regulation of this enzyme. 相似文献
93.
Background
The concentration of iron in the brain increases with aging. Furthermore, it has also been observed that patients suffering from neurological diseases (e.g. Parkinson, Alzheimer…) accumulate iron in the brain regions affected by the disease. Nevertheless, it is still not clear whether this accumulation is the initial cause or a secondary consequence of the disease. Free iron excess may be an oxidative stress source causing cell damage if it is not correctly stored in ferritin cores as a ferric iron oxide redox-inert form.Scope
Both, the composition of ferritin cores and their location at subcellular level have been studied using analytical transmission electron microscopy in brain tissues from progressive supranuclear palsy (PSP) and Alzheimer disease (AD) patients.Major conclusions
Ferritin has been mainly found in oligodendrocytes and in dystrophic myelinated axons from the neuropili in AD. In relation to the biomineralization of iron inside the ferritin shell, several different crystalline structures have been observed in the study of physiological and pathological ferritin. Two cubic mixed ferric–ferrous iron oxides are the major components of pathological ferritins whereas ferrihydrite, a hexagonal ferric iron oxide, is the major component of physiological ferritin. We hypothesize a dysfunction of ferritin in its ferroxidase activity.General significance
The different mineralization of iron inside ferritin may be related to oxidative stress in olygodendrocites, which could affect myelination processes with the consequent perturbation of information transference. 相似文献94.
95.
Genetic evidence for posterior specification by convergent extension in the Xenopus embryo 总被引:2,自引:2,他引:0
Genetic studies substantiate that mesodermal convergent extension expressed behind the anteroposterior borderline, in the form of a gradient with the posterior apex after gastrulation, regulates morphogenesis of the posterior zone at the dorsal and dorso-lateral levels which is in full agreement with the model of dorsalization–caudalization. In contrast, how anteroposterior specification of mesodermal tissues occurs at the ventral and latero-ventral levels is not yet understood. 相似文献
96.
Several indices of reproductive skew, which quantify the degree of unequal partitioning of reproductive output among members
in an animal society, have been proposed. Here we point out the drawbacks of these indices. The most serious problem is the
dependence of the indices on mean reproductive success: skew values tend to be larger, as average numbers of offspring decrease,
due to random sampling error in numbers of offspring. Thus it is difficult to compare societies with different average lifetime
reproductive success using these indices, even though we have presented methods to calculate the expected reproductive skew
caused by random sampling error, especially when average numbers of offspring are small, as is often the case with cooperatively
breeding vertebrates. As an alternative, we propose using the spatial dispersion indices of population ecology (Morisita's
index or its standardized version) for the measurement of reproductive skew. These indices are almost independent of average
fecundity and have their own method of testing for random variation in offspring numbers.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
97.
The first recorded incidence of dicephalia in a bull shark Carcharhinus leucas is reported from a foetus collected by a fisherman in the Gulf of Mexico near Florida, U.S.A. External examination, Radiography and magnetic resonance imaging revealed a case of monosomic dicephalia where the axial skeleton and internal organs were found to divide into parallel systems anterior to the pectoral girdle resulting in two well‐developed heads. 相似文献
98.
Emma Sherratt Felicity J. Coutts Arne R. Rasmussen Kate L. Sanders 《Evolution & development》2019,21(3):135-144
Snakes exhibit a diverse array of body shapes despite their characteristically simplified morphology. The most extreme shape changes along the precloacal axis are seen in fully aquatic sea snakes (Hydrophiinae): “microcephalic” sea snakes have tiny heads and dramatically reduced forebody girths that can be less than a third of the hindbody girth. This morphology has evolved repeatedly in sea snakes that specialize in hunting eels in burrows, but its developmental basis has not previously been examined. Here, we infer the developmental mechanisms underlying body shape changes in sea snakes by examining evolutionary patterns of changes in vertebral number and postnatal ontogenetic growth. Our results show that microcephalic species develop their characteristic shape via changes in both the embryonic and postnatal stages. Ontogenetic changes cause the hindbodies of microcephalic species to reach greater sizes relative to their forebodies in adulthood, suggesting heterochronic shifts that may be linked to homeotic effects (axial regionalization). However, microcephalic species also have greater numbers of vertebrae, especially in their forebodies, indicating that somitogenetic effects also contribute to evolutionary changes in body shape. Our findings highlight sea snakes as an excellent system for studying the development of segment number and regional identity in the snake precloacal axial skeleton. 相似文献
99.
Alpha-14 giardin (annexin E1), a member of the alpha giardin family of annexins, has been shown to localize to the flagella of the intestinal protozoan parasite Giardia lamblia. Alpha giardins show a common ancestry with the annexins, a family of proteins most of which bind to phospholipids and cellular membranes in a Ca2+-dependent manner and are implicated in numerous membrane-related processes including cytoskeletal rearrangements and membrane organization. It has been proposed that alpha-14 giardin may play a significant role during the cytoskeletal rearrangement during differentiation of Giardia. To gain a better understanding of alpha-14 giardin's mode of action and its biological role, we have determined the three-dimensional structure of alpha-14 giardin and its phospholipid-binding properties. Here, we report the apo crystal structure of alpha-14 giardin determined in two different crystal forms as well as the Ca2+-bound crystal structure of alpha-14 giardin, refined to 1.9, 1.6 and 1.65 Å, respectively. Although the overall fold of alpha-14 giardin is similar to that of alpha-11 giardin, multiwavelength anomalous dispersion phasing was required to solve the alpha-14 giardin structure, indicating significant structural differences between these two members of the alpha giardin family. Unlike most annexin structures, which typically possess N-terminal domains, alpha-14 giardin is composed of only a core domain, followed by a C-terminal extension that may serve as a ligand for binding to cytoskeletal protein partners in Giardia. In the Ca2+-bound structure we detected five bound calcium ions, one of which is a novel, highly coordinated calcium-binding site not previously observed in annexin structures. This novel high-affinity calcium-binding site is composed of seven protein donor groups, a feature rarely observed in crystal structures. In addition, phospholipid-binding assays suggest that alpha-14 giardin exhibits calcium-dependent binding to phospholipids that coordinate cytoskeletal disassembly/assembly during differentiation of the parasite. 相似文献
100.
Helicobacter pylori secretes a unique virulence factor, Tipα, that enters gastric cells and both stimulates the production of the TNF-α and activates the NF-κB pathway. The structures of a truncated version of Tipα (TipαN34) in two crystal forms are presented here. Tipα adopts a novel β1α1α2β2β3α3α4 topology that can be described as a combination of three domains. A first region consists in a short flexible extension, a second displays a dodecin-like fold and a third is a helical bundle domain similar to the sterile alpha motif (SAM). Analysis of the oligomerisation states of TipαN34 in the crystals and in solution suggests that the disulfide bridges could hold together Tipα monomers during their secretion in the gastric environment.