bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thyroid Hormone Causes Mitogen-Activated Protein Kinase-Dependent Phosphorylation of the Nuclear Estrogen Receptor
Authors: Tang Heng-Yuan , Lin Hung-Yun , Zhang Shenli , Davis Faith B. , Davis Paul J. 
Published: April 2004

AbstractActivated by thyroid hormone, the MAPK (ERK1/2) signaling pathway causes serine phosphorylation by MAPK of several nucleoproteins, including the nuclear thyroid hormone receptor β1. Because estrogen can activate MAPK and cause MAPK-dependent serine phosphorylation of nuclear estrogen receptor (ER)α, we studied whether thyroid hormone also promoted MAPK-mediated ERα phosphorylation. Human breast cancer (MCF-7) cells were incubated with physiological concentrations of l-T4 or 17β-estradiol (E2) for 15 min to 24 h, and nuclear ERα and serine-118-phosphorylated ERα were identified by Western blotting. Serine-118-phosphorylated ERα was recovered at 15 min in nuclei of MCF-7 cells exposed to either T4 or E2. The T4 effect was apparent at 15 min and peaked at 2 h, whereas the E2 effect was maximal at 4–6 h. T4-agarose was as effective as T4 in causing phosphorylation of ERα. T4 action on ERα was inhibited by PD 98059, an inhibitor of ERK1/2 phosphorylation, and by tetraiodothyroacetic acid, a T4 analog that blocks cell surface-initiated actions of T4 but is not itself an agonist. Electrophoretic mobility shift assay of nuclear extracts from T4-treated and E2-treated cells showed similar specific protein-DNA-binding. Indexed by [3H]thymidine incorporation and nuclear proliferating cell nuclear antigen, MCF-7 cell proliferation was stimulated by T4 and T4-agarose to an extent comparable with the effect of E2. This T4 effect was blocked by either PD 98059 or ICI 182,780, an ER antagonist. Thus, T4, like E2, causes phosphorylation by MAPK of nuclear ERα at serine-118 in MCF-7 cells and promotes cell proliferation through the ER by a MAPK-dependent pathway.
Dissolution media simulating the intralumenal composition of the small intestine: physiological issues and practical aspects
Authors: Vertzoni Maria , Fotaki Nikoletta , Nicolaides Eleftheria , Reppas Christos , Kostewicz Edmund , Stippler Erika , Leuner Christian , Dressman Jennifer 
Published: April 2004

Abstract
The objective of this study was to test various aspects of dissolution media simulating the intralumenal composition of the small intestine, including the suitability of the osmolality-adjusting agents and of the buffers, the substitution of crude sodium taurocholate (from ox bile) for pure sodium taurocholate and the substitution of partially hydrolysed soybean phosphatidylcholine for egg phosphatidylcholine. It was concluded that biorelevant media should contain sodium as the major cation species to better reflect the physiology. However, the use of non-physiologically relevant buffers is inevitable, especially for simulation of the fed state in the small intestine. The buffers used may affect the solubility product of weakly basic compounds with pKa(s) higher than about 5, the solubility of extremely highly lipophilic compounds due to salting in/out properties of the anion of the buffer and the stability of the dissolving compound. It is prudent in relevant situations to run an additional dissolution test in a modified fed state simulated intestinal fluid (FeSSIF) (or fasted state simulated intestinal fluid (FaSSIF), where applicable) containing alternative buffer species. Although a mixture of bile salts is physiologically more relevant than pure sodium taurocholate, this issue seems to be of practical importance in only a few cases. Adequate simulations in these cases will probably require the use of a number of pure substances and could substantially increase the cost of the test. Finally, unless the drug is extremely lipophilic (ca. logP &gt; 5), egg phosphatidylcholine can be substituted by partially hydrolysed soybean phosphatidylcholine.
A gallic acid derivative and polysaccharides with antioxidative activity from rose (Rosa rugosa) flowers
Authors: Ng T B , He J S , Niu S M , Pi Z F , Shao W , Liu F , Zhao L 
Published: April 2004

Abstract
In this study, the major antioxidant components of rose flower were identified. An aqueous extract of rose flowers was chromatographed on CM-cellulose in ammonium acetate buffer (10 mm, pH 4.5) to yield three un-adsorbed peaks F1, F2 and F3. Each of these peaks was subjected to gel filtration on Sephadex G75. F1 yielded two peaks, whereas both F2 and F3 gave rise to only a single peak. Spectroscopic studies using NMR and FTIR revealed that F3 is a gallic acid derivative. It exhibited the highest antioxidative potency. F1-a derived from F1 by gel filtration is mainly a polysaccharide-peptide complex with less potent antioxidative activity. F2 is a polysaccharide also with reduced antioxidant activity. This study demonstrates, for the first time, the presence of both gallic acid derivatives and polysaccharides as major antioxidant principles of the aqueous extract of rose flowers.
Coptidis Rhizoma: protective effects against peroxynitrite-induced oxidative damage and elucidation of its active components
Authors: Yokozawa Takako , Ishida Ai , Cho Eun Ju , Kim Hyun Young , Kashiwada Yoshiki , Ikeshiro Yasumasa 
Published: April 2004

Abstract
We have investigated the protective effects of Coptidis Rhizoma against peroxynitrite (ONOO−)-induced oxidative damage and have elucidated the active components of this preparation. In an invitro system, Coptidis Rhizoma extract scavenged ONOO− and its precursors, nitric oxide (NO) and superoxide anion (O2−). This scavenging activity was more marked for ONOO− than its precursors. In addition, against 3-morpholinosydnonimine-induced cellular damage, this extract significantly reduced cellular ONOO− formation and increased cell viability. In an in-vivo lipopolysaccharide plus ischaemia-reperfusion system that generated ONOO−, the administration of Coptidis Rhizoma extract at 50 and 100 mg kg−1/day for 30 days exerted greater inhibition of ONOO− than NO and O2−. This suggested that it acted as a direct scavenger of ONOO− rather than as a scavenger of its precursors. Moreover, the suppression of the activities of the antioxidative enzymes superoxide dismutase, catalase and glutathione peroxidase was significantly attenuated by the administration of Coptidis Rhizoma extract. Furthermore, the extract ameliorated renal dysfunction judged by decreasing serum urea nitrogen and creatinine levels. To elucidate the active components of Coptidis Rhizoma extract, we evaluated and compared the effects of the phenol plus alkaloid and alkaloid fractions on ONOO−-induced damage. We found that the alkaloid fraction consisting of berberine, palmatine and coptisine was the most effective at protecting against ONOO−. We confirmed that berberine (10 and 20 mg kg−1/day for 10 days), the main and most active alkaloid in Coptidis Rhizoma extract, was also protective, exerting NO-, O2−- and ONOO−-scavenging activities. This study suggested that Coptidis Rhizoma could protect against ONOO−-induced oxidative damage and that this effect was mainly attributable to the constituent alkaloids, especially berberine. This study is the first to demonstrate an antioxidative effect of alkaloids, including berberine, against ONOO−-induced damage.
Astilbin prevents concanavalin A-induced liver injury by reducing TNF-α production and T lymphocyte adhesion
Authors: Wang Jun , Zhao Ying , Xu Qiang 
Published: April 2004

Abstract
The aim of this study was to evaluate the effect of astilbin on concanavalin A (Con A)-induced hepatitis, a T cell-dependent model of liver injury. Con A administration resulted in a severe liver injury in mice, with a strong increment in spleen cell adhesion and liver infiltration of T cells, as well as in tumour necrosis factor (TNF)-α production. Against this liver injury, astilbin significantly inhibited the elevation in transaminase activity, reduced the TNF-α production, and improved the histological changes, including inflammatory infiltration, hepatocyte necrosis and degeneration and Kupffer cell hyperplasia. In addition, astilbin inhibited the adhesion of spleen cells and purified T lymphocytes isolated from the liver-injured mice to fibronectin, laminin and type IV collagen. Moreover, the adhesion of human Jurkat T cells to endothelial cell line ECV-304 was also inhibited by astilbin. These results suggest that the improvement of the T cell-mediated liver injury by astilbin may be related to the reduction in TNF-α production and in T cell adhesion to extracellular matrices and endothelial cells.
Pharmacokinetics of a new Autogel formulation of the somatostatin analogue lanreotide after a single subcutaneous dose in healthy volunteers
Authors: Antonijoan R M , Barbanoj M J , Cordero J A , Peraire C , Obach R , Vallès J , CheZérif-Cheikh R , Torres M-L , Bismuth F , Montes M 
Published: April 2004

Abstract
The pharmacokinetics/tolerability of lanreotide Autogel have been evaluated. Healthy volunteers (n = 24) first received immediate-release lanreotide as a single subcutaneous (s.c.) injection. After two days, 40 or 60 mg lanreotide Autogel was injected subcutaneously. Blood was sampled at various intervals for 56 days. Systemic/local adverse events and changes in biological profile/vital signs were recorded. Lanreotide Autogel produced a prolonged-release pharmacokinetic profile: mean area under the serum concentration-time curve from time 0 to infinity (AUC) was 53.73 + 8.99 and 79.48 + 13.06 ng mL−1 day for 40 and 60 mg, respectively, mean peak serum concentration (Cmax) was 4.38 + 2.91 and 5.71 + 3.52 ng mL−1, respectively, median time to reach Cmax (minimum-maximum) was 0.50 (0.083–18.0) and 0.38 (0.083–9.01) days, respectively, mean apparent elimination half-life was 21.63 + 9.42 and 22.01 + 9.87 days, respectively, and relative bioavailability was 0.93 + 0.12 and 0.82 + 0.15, respectively. Thus, lanreotide Autogel exhibited linear pharmacokinetics for the doses studied. Pharmacokinetic profiles were similar in both genders, apart from statistically significant differences in Cmax and Cmax/AUC. The Autogel formulation of lanreotide was well tolerated, with systemic adverse events being mild/moderate. Erythema and a painless subcutaneous induration were the most common local adverse events. Lanreotide Autogel provided a prolonged dosing interval and good tolerability for treating acromegaly and carcinoid syndrome.
Absorption, distribution and excretion of 14C-levofloxacin after single oral administration in albino and pigmented rats: binding characteristics of levofloxacin-related radioactivity to melanin in vivo
Authors: Tanaka Makoto , Ono Chiho , Yamada Masayoshi 
Published: April 2004

Abstract
After single oral administration of 14C-levofloxacin at a dose of 20 mg kg−1 under non-fasting conditions, the absorption, distribution and excretion of radioactivity were studied in albino and pigmented rats. Good penetration of radioactivity into tissues was indicated by higher concentrations in most tissues compared with serum and there were no quantitative differences in the distribution of radioactivity between albino and pigmented rats except for melanin-containing tissues such as the uveal tract of eyes and hair follicles. There was selective and strong binding of drug-related radioactivity to these tissues in pigmented rats. The uveal tract concentrations reached the maximum value (Cmax) of 26.33 + 0.75 μg eq.g−1 at 24 h after dosing and declined slowly with a terminal half-life of 468.1 h (19.5 days). The uveal tract concentration at 12 weeks was 0.73 + 0.12 μg eq.g−1, which is c. 1/36 of Cmax. The AUC0-∞ for the uveal tract was 12.58 mg h−1 g−1. The uveal tracts separated from one eye of each rat were extracted with 0.067 m phosphate buffer (pH 7.4) and 1m HCl/EtOH (30:70), successively. In pigmented rats, approximately 85–48% of radioactivity bound to the uveal tract was released from the tissue by the washing procedures. Most of the eluted radioactivity was released with 1m HCl/EtOH (30:70), indicating that the binding to melanin is reversible, and hydrophobic and electrostatic interactions play an important role in the binding of levofloxacin and/or its metabolites with melanin-containing ocular tissues. Only unchanged drug was detected in the extracts of the uveal tracts. The concentrations and half-life of radioactivity in the uveal tract after dosing of 14C-levofloxacin were found to be much lower and shorter than those after dosing of 14C-chloroquine. It is unlikely that levofloxacin causes toxicity because of its much lower affinity to melanin-containing ocular tissues and shorter duration of therapy compared to chloroquine.
Design, synthesis and properties of novel iron(III)-specific fluorescent probes
Authors: Luo Wei , Ma Yong M , Quinn Peter J , Hider Robert C , Liu Zu D 
Published: April 2004

Abstract
Bidentate chelators such as hydroxypyridinones and hydroxypyranones are highly iron selective. The synthesis of two novel fluorescent probes N-[2-(3-hydroxy-2-methyl-4-oxopyridin-1(4H)-yl)ethyl]-2-(7-methoxy-2-oxo-2H-chromen-4-yl)acetamide (CP600) and N-[(3-hydroxy-6-methyl-4-oxo-4H-pyran-2-yl)methyl]-2-(7-methoxy-2-oxo-2H-chromen-4-yl)acetamide (CP610) is reported. The method involves coupling the bidentate ligands, 3-hydroxypyridin-4-one and 3-hydroxypyran-4-one, with the well-characterised fluorescent probe methoxycoumarin. Fluorescence emission of both probes at 380 nm is readily quenched by Fe3+. The fluorescence was quenched to a greater extent by Fe3+ than by Mn2+, Co2+, Zn2+, Ca2+, Mg2+, Na+ and K+ and to approximately the same extent as Cu2+. Comparison of the fluorescence-quenching ability by a range of metal ions on CP600 and CP610 and the hexadentate chelator, calcein, under in-vitro conditions, demonstrated advantages of the two novel fluorescent probes with respect to both iron(III) sensitivity and selectivity. Chelation of iron(III) by CP600 and CP610 leads to the formation of a complex with a metal-to-ligand ratio of 1:3. Fluorescence is quenched on formation of such complexes. These probes possess a molecular weight less than 400 and thus they are predicted to permeate biological membranes by passive diffusion, and have potential for reporting intracellular organelle labile iron levels.
Delivery systems for bone growth factors — the new players in skeletal regeneration
Authors: Rose Felicity R A J , Hou Qingpu , Oreffo Richard O C 
Published: April 2004

Abstract
Given the challenge of an increasing elderly population, the ability to repair and regenerate traumatised or lost tissue is a major clinical and socio-economic need. Pivotal in this process will be the ability to deliver appropriate growth factors in the repair cascade in a temporal and tightly regulated sequence using appropriately designed matrices and release technologies within a tissue engineering strategy. This review outlines the current concepts and challenges in growth factor delivery for skeletal regeneration and the potential of novel delivery matrices and biotechnologies to influence the healthcare of an increasing ageing population.
Polarity and lipid raft association of the components of the ciliary neurotrophic factor receptor complex in Madin-Darby canine kidney cells
Authors: Buk Deborah M. , Waibel Michaela , Braig Claudia , Martens Astrid S. , Heinrich Peter C. , Graeve Lutz 
Published: April 2004

Ciliary neurotrophic factor (CNTF) signals via a tripartite receptor complex consisting of the glycosyl-phosphatidylinositol (GPI)-anchored CNTF receptor (CNTF-R), the leukaemia inhibitory factor receptor (LIF-R) and the interleukin-6 (IL-6) signal transducer gp130. We have recently reported that gp130 is endogenously expressed in the polarised epithelial model cell line Madin-Darby canine kidney (MDCK) and we have demonstrated a preferential basolateral localisation of this protein. In the present study we show that MDCK cells also express the LIF-R and respond to stimulation with human LIF by activation of tyrosine phosphorylation of signal transducer and activator of transcription-3 (STAT3), both however in an unpolarised fashion. This suggests that MDCK cells may be target cells for LIF. We have furthermore stably expressed the human CNTF-R in MDCK cells and by two different assays we found an apical localisation. Consistent with these findings, stimulation of CNTF-R-positive cells resulted only in an activation of STAT3 when CNTF was added apically. These data demonstrate that each subunit of the CNTF receptor complex has a distinct distribution in polarised cells which may reflect the different roles the respective cytokines play in vivo.Since it is currently believed that lipid rafts are involved in signal transduction as well as protein sorting we studied the association of the three receptor complex components with membrane rafts using different protocols. Whereas the CNTF-R cofractionated quantitatively with lipid rafts independently of the method used, gp130 and the LIF-R were found to associate with lipid rafts only partially when detergents were used for isolation. These findings could indicate that either the three receptor complex subunits are localised to the same kind of raft but with different affinities to the liquid-ordered environment, or that they are localised to different types of rafts. CNTF-, LIF-, and IL-6-dependent STAT3 activation was sensitive to the cholesterol-depleting drug methyl-β-cyclodextrin (MCD) suggesting that the integrity of lipid rafts is important for IL-6-type cytokine-induced STAT activation.
The most severe forms of Perthes’ disease associated with the homozygous Factor V Leiden mutation
Authors: Szepesi K. , Pòsán E. , Hársfalvi J. , Ajzner É , Szücs G. , Gáspár L. , Csernátony Z. , Udvardy M. 
Published: April 2004

It has recently been postulated that thrombophilia may have a role in the aetiology of Perthes’ disease. The published reports, however, remain conflicting. In this study a retrospective analysis of the coagulation parameters was made in 47 patients with Perthes’ disease and the results compared with the clinical data. Five patients with Factor V Leiden mutation were found (10.6%) and surprisingly four of them had a homozygous pattern. These four patients showed the most severe form of the disease, Catterall group IV, with flattening of the entire epiphysis, involvement of the metaphysis, shortening and broadening of the femoral neck, trochanteric overgrowth and developed mushroom-shaped aspherical laterally displaced femoral heads in dysplastic acetabula. We would like to suggest that the homozygous form of Factor V Leiden mutation has some role in the clinical course of Perthes’ disease and particularly its most severe form.
The accuracy of image-guided knee replacement based on computed tomography
Authors: Nabeyama R. , Matsuda S. , Miura H. , Mawatari T. , Kawano T. , Iwamoto Y. 
Published: April 2004

Our study evaluated the accuracy of an image-guided total knee replacement system based on CT with regard to preparation of the femoral and tibial bone using nine limbs from five cadavers. The accuracy was assessed by direct measurement using an extramedullary alignment rod without radiographs. The mean angular errors of the femur and tibia, which represent angular gaps from the real mechanical axis in the coronal plane, were 0.3° and 1.1°, respectively. The CT-based system, provided almost perfect alignment of the femoral component with less than 1° of error and excellent alignment with less than 3° of error for the tibial component. Our results suggest that standardisation of knee replacement by the use of this system will lead to improved long-term survival of total knee arthroplasty.
The Ferguson medial approach for open reduction of developmental dysplasia of the hip
Authors: Kiely N. , Younis U. , Day J.B. , Meadows T.M. 
Published: April 2004

The results of the Ferguson medial approach for open reduction of developmental dysplasia of the hip (DDH) were reviewed for 49 hips with a follow-up of more than 48 months. The mean age at operation was 12.3 months (6 to 23). The mean length of clinical and radiological follow-up was 82 months (48 to 148). Three redislocations occurred. Group I avascular necrosis according to the classification of Kalamchi and MacEwen was seen in four hips, group II in two hips and group III in one hip; 92% of the hips were classified as Severin class I and II. The acetabular index and centre edge (CE) angles were within normal limits at final follow-up, but were still significantly different from the unaffected side. We conclude that the Ferguson procedure is safe and reliable for low dislocations in children aged six to 18 months.
Inter- and intra-measurer error in the measurement of Reimers’ hip migration percentage
Authors: Faraj S. , Atherton W. G. , Stott N. S. 
Published: April 2004

Reimers’ hip migration percentage is commonly used to document the extent of subluxation of the hip in children with spasticity. In this study, two measurers, with six months paediatric orthopaedic experience, measured the migration percentage on 44 pelvic radiographs of children with cerebral palsy, aged between two and eight years. Unknown to the measurers, each radiograph was duplicated, giving 22 non-identical radiographs (44 hips) which were measured twice at time 0 and twice six weeks later. The intra-measurer, intra-sessional absolute differences between the first and second measurements ranged from 0% to 23%, with median values of 2.5% to 3.6%. The intra-sessional median absolute differences were not statistically different between the two measurers and measuring sessions (p = 0.42, Kruskal-Wallis test). The inter-sessional absolute differences for measurements made by the same measurers ranged from 0% to 18% with a median absolute difference of 1.7% to 3.2%. Overall, only 5% of the intra-measurer measurement differences, within and between sessions, were above 13%. Repeated measurements by one measurer over time must, therefore, vary by more than 13% in order to be 95% confident of a true change. The inter-measurer error was higher with median absolute differences between the two measurers’ measurements of the same hip of 3.25% to 5% (0% to 26%) and a 95th upper confidence interval of 21% to 23%. Averaging the four separate measurements over the two sessions reduced the inter-measurer error to a median absolute difference of 2.8%, but did not improve the 95th upper confidence interval, which measured 22.4%. Such inter-measurer errors may be clinically unacceptable.
The effects of calcitonin on acute bone loss after pertrochanteric fractures
Authors: Karachalios T. , Lyritis G. P. , Kaloudis J. , Roidis N. , Katsiri M. 
Published: April 2004

We investigated the effect of calcitonin in the prevention of acute bone loss after a pertrochanteric fracture and its ability to reduce the incidence of further fractures in the same patient. Fifty women aged between 70 and 80 years who had a pertrochanteric fracture of the hip were randomly allocated to group A (200 IU of nasal salmon calcitonin daily for three months) or group B (placebo). Patients in group A showed a significantly higher level of total alkaline phosphatase and osteocalcin on the 15th day after injury and a significantly higher level of bone alkaline phosphatase on the 90th day after surgery. These patients also had significantly lower levels of urinary C-telopeptide (CrossLaps) on the 15th, 45th and 90th days after injury and lower levels of urinary hydroxyproline on the 15th and 45th days after injury. Patients in group A had significantly higher bone mineral density at all recorded sites except the greater trochanter at three months and one year after operation. After a four-year period of clinical observation, five patients (24%) in group B sustained a new fracture, in four of whom (20%) it was of the contralateral hip. Our findings show that calcitonin reduces acute bone loss in patients with pertrochanteric fractures and may prevent the occurrence of new fractures of the contralateral hip in the elderly.