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131.
Walter W. Hauck Anthony J. DeStefano William E. Brown Erika S. Stippler Darrell R. Abernethy William F. Koch Roger L. Williams 《AAPS PharmSciTech》2009,10(1):21-26
The US Pharmacopeial Convention has been evaluating its performance verification tests (PVT) for several years. These tests
help ensure the integrity of the US Pharmacopeia performance test when a dissolution procedure, as described in General Chapter Dissolution <711>, is relied upon to test a nonsolution orally administered dosage form. One result of the evaluation is a change in
the PVT criterion from one based on individual tablet results to one based on the mean and variability of a set of tablets.
This paper describes the new PVT and its criterion and how its acceptance limits are derived from results of a collaborative
study, explains a two-stage option for the test, and presents operating characteristics. 相似文献
132.
Steenvoorden MM Tolboom TC van der Pluijm G Löwik C Visser CP DeGroot J Gittenberger-DeGroot AC DeRuiter MC Wisse BJ Huizinga TW Toes RE 《Arthritis research & therapy》2006,8(6):R165-10
The healthy synovial lining layer consists of a single cell layer that regulates the transport between the joint cavity and the surrounding tissue. It has been suggested that abnormalities such as somatic mutations in the p53 tumor-suppressor gene contribute to synovial hyperplasia and invasion in rheumatoid arthritis (RA). In this study, expression of epithelial markers on healthy and diseased synovial lining tissue was examined. In addition, we investigated whether a regulated process, resembling epithelial to mesenchymal transition (EMT)/fibrosis, could be responsible for the altered phenotype of the synovial lining layer in RA. Synovial tissue from healthy subjects and RA patients was obtained during arthroscopy. To detect signs of EMT, expression of E-cadherin (epithelial marker), collagen type IV (indicator of the presence of a basement membrane) and alpha-smooth muscle actin (alpha-sma; a myofibroblast marker) was investigated on frozen tissue sections using immunohistochemistry. Fibroblast-like synoviocytes (FLSs) from healthy subjects were isolated and subjected to stimulation with synovial fluid (SF) from two RA patients and to transforming growth factor (TGF)-beta. To detect whether EMT/fibrotic markers were increased, expression of collagen type I, alpha-sma and telopeptide lysylhydroxylase (TLH) was measured by real time PCR. Expression of E-cadherin and collagen type IV was found in healthy and arthritic synovial tissue. Expression of alpha-sma was only found in the synovial lining layer of RA patients. Stimulation of healthy FLSs with SF resulted in an upregulation of alpha-sma and TLH mRNA. Collagen type I and TLH mRNA were upregulated after stimulation with TGF-beta. Addition of bone morphogenetic protein (BMP)-7 to healthy FLS stimulated with SF inhibited the expression of alpha-sma mRNA. The finding that E-cadherin and collagen type IV are expressed in the lining layer of healthy and arthritic synovium indicates that these lining cells display an epithelial-like phenotype. In addition, the presence of alpha-sma in the synovial lining layer of RA patients and induction of fibrotic markers in healthy FLSs by SF from RA patients indicate that a regulated process comparable to EMT might cause the alteration in phenotype of RA FLSs. Therefore, BMP-7 may represent a promising agent to counteract the transition imposed on synoviocytes in the RA joint. 相似文献
133.
Sandrine Souquire Frdric Bibollet-Ruche David L. Robertson Maria Makuwa Cristian Apetrei Richard Onanga Christopher Kornfeld Jean-Christophe Plantier Feng Gao Katharine Abernethy Lee J. T. White William Karesh Paul Telfer E. Jean Wickings Philippe Mauclre Preston A. Marx Franoise Barr-Sinoussi Beatrice H. Hahn Michaela C. Müller-Trutwin Franois Simon 《Journal of virology》2001,75(15):7086-7096
Mandrillus sphinx, a large primate living in Cameroon and Gabon and belonging to the Papionini tribe, was reported to be infected by a simian immunodeficiency virus (SIV) (SIVmndGB1) as early as 1988. Here, we have identified a second, highly divergent SIVmnd (designated SIVmnd-2). Genomic organization differs between the two viral types; SIVmnd-2 has the additional vpx gene, like other SIVs naturally infecting the Papionini tribe (SIVsm and SIVrcm) and in contrast to the other SIVmnd type (here designated SIVmnd-1), which is more closely related to SIVs infecting l'hoest (Cercopithecus lhoesti lhoesti) and sun-tailed (Cercopithecus lhoesti solatus) monkeys. Importantly, our epidemiological studies indicate a high prevalence of both types of SIVmnd; all 10 sexually mature wild-living monkeys and 3 out of 17 wild-born juveniles tested were infected. The geographic distribution of SIVmnd seems to be distinct for the two types: SIVmnd-1 viruses were exclusively identified in mandrills from central and southern Gabon, whereas SIVmnd-2 viruses were identified in monkeys from northern and western Gabon, as well as in Cameroon. SIVmnd-2 full-length sequence analysis, together with analysis of partial sequences from SIVmnd-1 and SIVmnd-2 from wild-born or wild-living mandrills, shows that the gag and pol regions of SIVmnd-2 are closest to those of SIVrcm, isolated from red-capped mangabeys (Cercocebus torquatus), while the env gene is closest to that of SIVmnd-1. pol and env sequence analyses of SIV from a related Papionini species, the drill (Mandrillus leucophaeus), shows a closer relationship of SIVdrl to SIVmnd-2 than to SIVmnd-1. Epidemiological surveys of human immunodeficiency virus revealed a case in Cameroon of a human infected by a virus serologically related to SIVmnd, raising the possibility that mandrills represent a viral reservoir for humans similar to sooty mangabeys in Western Africa and chimpanzees in Central Africa. 相似文献
134.
Rogers ME Abernethy K Bermejo M Cipolletta C Doran D McFarland K Nishihara T Remis M Tutin CE 《American journal of primatology》2004,64(2):173-192
The objective of this paper is to collate information on western gorilla diet from six study sites throughout much of their current range, including preliminary information from two sites (Afi and Lossi), where studies of diet have begun only recently. Food lists were available from each site, derived from indirect signs of gorilla feeding (such as feces), with some observational data. Important staple, seasonal, and fallback foods have been identified, and a number of striking similarities across sites have been revealed based on a much larger data set than was previously available. It was confirmed that the western gorilla diet is always eclectic, including up to 230 items and 180 species. The greatest diversity is found among the fruit species eaten, fruit being included in western gorilla diets from all sites and throughout most or all of the year. Eight plant families provide important foods at five, or all six, sites, suggesting that it may be possible in the future to predict which habitats are the most suitable for gorillas. Gorillas exploit both rare and common forest species. Similarities and differences among sites can be explained superficially on the basis of geography and the past history of the forest. Gorilla density across sites appears to be most affected by the density of monocotyledonous bulk food plants, but its relationship to the density of important tree food species has yet to be tested. 相似文献
135.
136.
Boot EP Koning GA Storm G Wagenaar-Hilbers JP van Eden W Everse LA Wauben MH 《Arthritis research & therapy》2005,7(3):R604-R615
T cells have an important role during the development of autoimmune diseases. In adjuvant arthritis, a model for rheumatoid
arthritis, we found that the percentage of CD4+ T cells expressing the activation marker CD134 (OX40 antigen) was elevated before disease onset. Moreover, these CD134+ T cells showed a specific proliferative response to the disease-associated epitope of mycobacterial heat shock protein 60,
indicating that this subset contains auto-aggressive T cells. We studied the usefulness of CD134 as a molecular target for
immune intervention in arthritis by using liposomes coated with a CD134-directed monoclonal antibody as a drug targeting system.
Injection of anti-CD134 liposomes subcutaneously in the hind paws of pre-arthritic rats resulted in targeting of the majority
of CD4+CD134+ T cells in the popliteal lymph nodes. Furthermore, we showed that anti-CD134 liposomes bound to activated T cells were not
internalized. However, drug delivery by these liposomes could be established by loading anti-CD134 liposomes with the dipalmitate-derivatized
cytostatic agent 5'-fluorodeoxyuridine. These liposomes specifically inhibited the proliferation of activated CD134+ T cells in vitro, and treatment with anti-CD134 liposomes containing 5'-fluorodeoxyuridine resulted in the amelioration of adjuvant arthritis.
Thus, CD134 can be used as a marker for auto-aggressive CD4+ T cells early in arthritis, and specific liposomal targeting of drugs to these cells via CD134 can be employed to downregulate
disease development. 相似文献
137.
T-cell activation is considered to be an important element in the pathogenesis of psoriasis, a human skin disease characterized by keratinocyte hyperproliferation, altered keratinocyte differentiation and inflammation of the dermis and epidermis. Mice homozygous for the flaky skin (fsn) mutation develop a skin disorder that has histopathological and biochemical features resembling some forms of psoriasis. It has been reported recently that peripheral lymph nodes (PLN) in fsn/fsn mice exhibit various abnormalities in T-cell development suggestive of dysregulated T- and B-cell activation. In the present study, the expression of the inducible T-cell activation antigens CD69 and IL-2 receptor alpha chain (CD25) on PLN cells from fsn/fsn mice and their phenotypically normal littermates is examined. Expression of CD69 was significantly increased on PLN cells in fsn/fsn mice (mean +/- SD, 49.9 +/- 14.7% of cells) compared with control mice (14.6 +/- 4.2%). Analysis of CD4+ and CD8+ T cell subsets revealed that expression of CD69 in fsn/fsn PLN was significantly biased toward CD8+ cells. Although expression of CD25 was preferentially associated with CD4+ rather than CD8+ cells in both fsn/fsn and control PLN, with most CD4+ CD25+ cells being CD25hi, the proportion of CD4+ cells expressing CD25 was higher in fsn/fsn than control PLN. In contrast, CD25 was expressed by 2-3% of CD8+ PLN cells in both fsn/fsn and control mice and CD25hi cells accounted for < 1% of CD8+ cells in fsn/fsn PLN. The paucity of CD25 on CD8+ cells in fsn/fsn PLN did not appear to be due to a defect in the ability of these cells to upregulate CD25, because T cell receptor stimulation in vitro induced high expression of CD25 on both CD4+ and CD8+ cells. A striking and consistent finding was that most CD8+ cells in fsn/fsn PLN expressed high levels of IL-2R beta chain (CD122). In contrast, CD122 was expressed at low levels on CD8+ cells in control mice. Analysis of PLN cells from newborn fsn/fsn mice revealed that the high expression of CD122 on CD8+ cells was established by 2 weeks of age, prior to the appearance of clinical skin disease. These data indicate that large numbers of T cells in fsn/fsn mice are activated and reinforce the view that fsn is an important regulator of lymphocyte development and function. The relationship between T-cell activation and flaky skin disease in these mice remains to be established. 相似文献
138.
K Kertesz-Chaloupková PJ Walser JD Granado M Aebi U Kües 《Fungal genetics and biology : FG & B》1998,23(1):95-109
Monokaryotic mycelia of the homobasidiomycete Coprinus cinereus form asexual spores (oidia) constitutively in abundant numbers. Mycelia with mutations in both mating type loci (Amut Bmut homokaryons) also produce copious oidia but only when exposed to blue light. We used such an Amut Bmut homokaryon to define environmental and inherent factors that influence the light-induced oidiation process. We show that the Amut function causes repression of oidiation in the dark and that light overrides this effect. Similarly, compatible genes from different haplotypes of the A mating type locus repress sporulation in the dark and not in the light. Compatible products of the B mating type locus reduce the outcome of light on A-mediated repression but the mutated B function present in the Amut Bmut homokaryons is not effective. In dikaryons, the coordinated regulation of asexual sporulation by compatible A and B mating type genes results in moderate oidia production in light. Copyright 1998 Academic Press. 相似文献
139.
Sabaté M Ligthart J Deshpande N DeFeyter P Serruys P 《International journal of cardiovascular interventions》1998,1(2):109-112
We report a case of implantation of a new design of stent which allows creation of a double-hemispheric lumen for the treatment of a bifurcational stenosis. The unfavourable outcome following the implantation of this stent is described. 相似文献
140.
David L. Thacker Darrell R. Abernethy Arthur Raines David A. Flockhart 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1998,710(1-2):149-155
A method is described for the measurement of 5,5-diphenylbarbituric acid in plasma using high-performance liquid chromatography with UV detection. Briefly, the compounds are separated on a C18 reversed-phase column using a mobile phase of 50 mM sodium acetate (pH 4.5) and methanol. The flow-rate is 1.0 ml/min and 25 μl are injected and detected at 215 nm. The method is specific and sensitive in the range of concentrations tested, with a limit of quantification of 0.25 μg/ml. The calibration curves are linear for concentrations between 0.25 and 10 μg/ml. Intra-day and inter-day coefficients of variation are less than 8.5 and 10.5%, respectively, over the linear range. Intra-day and inter-day bias are less than 7.0 and 8.0%, respectively. A pharmacokinetic study conducted in male Beagle dogs administered 10 mg/kg of 1,3-dimethoxymethyl-5,5-diphenylbarbituric acid or 8 mg/kg of 5,5-diphenylbarbituric acid intravenously demonstrates the utility of this method. 相似文献