bluuebunny/crossref_metadata_2025_split huggingface dataset:
Application of poly(acrylic acid) superporous hydrogel microparticles as a super-disintegrant in fast-disintegrating tablets
Authors: Yang Shicheng , Fu Yurong , Jeong Seong Hoon , Park Kinam 
Published: April 2004

Abstract
Poly(acrylic acid) superporous hydrogel (SPH) microparticles possessing a unique porous structure were used as a wicking agent to decrease disintegration time of fast-disintegrating tablets (FDTs). The compression behaviour of poly(acrylic acid) SPH microparticles was evaluated using the Kawakita equation. Effects of various SPH microparticle sizes and a 19-run fractional factorial design were evaluated. The factorial design was based on four factors consisting of ketoprofen, SPH microparticle, filler, and tableting pressure, and each factor contained three levels on the disintegration time and tensile strength of the prepared FDTs. The poly(acrylic acid) SPH microparticles existed in an amorphous state and swelled approximately 80-times in distilled water and 50-times in pH 6.8 0.2 m phosphate buffer. The compressibility of SPH microparticles increased significantly as the microparticle size increased. The FDTs made of SPH microparticles in the range of 75–106 μm showed the fastest disintegration time and higher tensile strength. SPH microparticle, tableting pressure and ketoprofen had significant effects on disintegration time and tensile strength of ketoprofen FDTs. The FDTs that were prepared with 2.5% w/w SPH microparticles of 75–106 μm at 63 MPa pressure possessed a tensile strength of 84.4+4.1 N cm−2 and disintegrated in 15.0+2.0 s. It was concluded that the poly(acrylic acid) SPH microparticles could serve as a good super-disintegrant decreasing the disintegration time of FDTs.
Effects of dialkoxylphenyl compounds with oxime group on macrophage function and the proliferation of lymphocytes
Authors: Yoo Eun Sook , Yoo Eun Sook , Son Ho Jung , Park Joon Seok , Kim Ae Ra , Baik Kyong Up , Park Myung Hwan , Cho Jae Youl , Cho Jae Youl 
Published: April 2004

Abstract
Dialkoxyphenyl compounds have been reported to possess anti-inflammatory activity through inhibition of phosphodieseterase (PDE) type IV. In this study, a series of derivatives of dialkoxyphenyl compounds with an oxime group, which is generally known to be one of the biologically active functional groups, were prepared and evaluated for their ability to inhibit the production of inflammatory mediators in activated macrophages and the proliferation of lymphocytes. The structure–activity relationship (SAR) study with 12 compounds on tumour necrosis factor (TNF)-α inhibition, analysed by the oxime geometry and different size of spacers between the oxime and phenyl group, indicated that there might be at least three possible hydrogen bonding sites in the inhibitor binding pocket of PDE IV. Of them, compound 6 clearly displayed the highest inhibitory effect on in-vitro TNF-α production from lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Compound 6 also suppressed in-vivo TNF-α release from LPS-primed mice, a level comparable with that of the standard PDE IV inhibitor, rolipram. In addition, oxime compounds also significantly inhibited both nitric oxide production from activated RAW264.7 cells and T lymphocyte proliferation elicited by concanavalin A but not IL-2. The data suggest that the oxime group may act as a functional group, capable of interacting with the inhibitor-binding pocket of target PDE IV. Therefore, it is conceivable that compound 6 may have the potential either to be developed as a new anti-inflammatory drug or to be used to develop more potent analogues.
Influence of intravenous methylprednisolone pulse treatment on the disposition of ciclosporin and hepatic CYP3A activity in rats
Authors: Konishi Hiroki , Sumi Masaki , Minouchi Tokuzo , Yamaji Akira , Sumi Masaki , Shibata Nobuhito , Takada Kanji 
Published: April 2004

Abstract
We examined the effects of high-dose methylprednisolone (MP) on the disposition of ciclosporin (CsA) and hepatic microsomal CYP3A activity using rats. Methylprednisolone sodium succinate (MPS), a prodrug of MP, was intravenously administered as repeated doses (66.3 mg kg−1) for 3 days or as a single dose. In MP-treated rats, a significant increase was observed in the total body clearance (CLtot) and elimination rate constant (Ke) of intravenously administered CsA. The enzyme activities of triazolam hydroxylations and erythromycin N-demethylation in hepatic microsomes were also enhanced by about 50% by MP treatment, suggesting that the alteration in the CsA pharmacokinetics was due to significant induction of the hepatic CYP3A responsible for the metabolic conversion of CsA. In contrast, no significant changes in the values of CLtot and Ke were found following a single treatment with MP. On the other hand, MP inhibited the CYP3A-mediated triazolam hydroxylations in a concentration-dependent manner. The difference between the in-vivo and in-vitro inhibitory behaviours of MP was attributed to the rapid elimination of MP after biotransformation from MPS because the plasma MP concentration decreased with a half-life of 15 min immediately after reaching a level close to the inhibition constant for the triazolam 4-hydroxylation reaction (32.4 μm). Although there is a general consideration that MP cannot act as an enzyme inducer at maintenance doses, the present results strongly suggest that high-dose MP is likely to interact pharmacokinetically with CsA by inducing hepatic CYP3A. These results may provide basic explanations for the clinical experience that blood CsA levels are reduced during MP pulse therapy.
Glycyrrhetic acid-loaded microparticles: liver-specific delivery and therapeutic potential against carbon tetrachloride-induced hepatitis
Authors: Takahashi Hiroaki , Onishi Hiraku , Machida Yoshiharu 
Published: April 2004

Abstract
The microparticles (MPs) of an anti-hepatotoxic drug, glycyrrhetic acid (GLA), were prepared using poly(dl-lactic acid-co-glycolic acid) as a drug carrier, and their in-vitro properties, biodistribution and therapeutic effects were investigated. The MPs showed a particle diameter distribution of 1.0–1.4 μm and a drug content of approximately 10% (w/w). In the in-vitro release in a mixture of methanol and phosphate-buffered saline pH 7.4 (3:7, v/v), slow release was observed after an initial burst release of approximately 30% (w/w). After i.v. administration of MPs in normal mice, GLA was mainly distributed to the liver. After i.v. administration in normal mice, the MPs maintained a much higher liver concentration than did GLA solution, and the plasma concentration also tended to be higher for MPs than for GLA solution. As to therapeutic effect, the liver was damaged by repeated injection of carbon tetrachloride (CCl4) in mice every 48 h, and the drugs were administered intravenously as a single dose 3 h after the first injection of CCl4. At 10 mg GLA eq. kg−1, the MPs significantly suppressed the plasma level of glutamic pyruvic transaminase for at least 141 h after administration, while GLA solution did not become significantly effective within 45 h post-administration. MPs are suggested as a possible useful system to prolong the therapeutic effect of GLA.
Involvement of thromboxane A2 (TXA2) in the early stages of oleic acid-induced lung injury and the preventive effect of ozagrel, a TXA2 synthase inhibitor, in guinea-pigs
Authors: Ishitsuka Yoichi , Moriuchi Hiroshi , Hatamoto Keita , Takase Junko , Irikura Mitsuru , Irie Tetsumi , Yang Changqing , Golbidi Saeid 
Published: April 2004

Abstract
An intravenous injection of oleic acid into animals can produce a lung injury with hypoxaemia and pulmonary vascular hyper-permeability. Although oleic acid lung injury is used as a model of acute respiratory distress syndrome (ARDS), the precise mechanisms of the lung injury are still unclear. We have investigated whether thromboxane A2 (TXA2) participated in the lung injury and have evaluated the efficacy of ozagrel, a TXA2 synthase inhibitor, on the lung injury in guinea-pigs. Oleic acid injection increased the plasma level of TXB2, a stable metabolite of TXA2, and the time-course of plasma TXB2 was similar to that of the decreased partial oxygen pressure of arterial blood (Pao2) induced with oleic acid. Ozagrel administered intravenously 30 min before oleic acid injection prevented the decrease in Pao2 and pulmonary vascular hyper-permeability. It also prevented increases in lactate dehydrogenase activity, a measure of lung cell injury, TXB2 and its weight ratio to 6-keto prostaglandin F1 α in bronchoalveolar lavage fluid. Although ozagrel administered simultaneously with oleic acid ameliorated the decrease in Pao2, post treatment showed little effect. We suggest that TXA2 participated in the oleic acid lung injury, as an “early phase” mediator, and rapidly-acting TXA2 synthase inhibitors were effective in the prevention of acute lung injury.
Cetraxate raises levels of calcitonin gene-related peptide and substance P in human plasma
Authors: Katagiri Fumihiko , Sato Yuhki , Itoh Hiroki , Takeyama Masaharu 
Published: April 2004

Abstract
Cetraxate hydrochloride (cetraxate), an anti-ulcer drug, produces a dose-related increase in mucosal blood flow. Recently, it was found that capsaicin-sensitive afferent nerves play an important role in gastric mucosal defence. Capsaicin stimulates afferent nerves and enhances the release of calcitonin gene-related peptide (CGRP) and substance P in the stomach. We studied the effect of cetraxate on human plasma CGRP and substance P in healthy subjects. Cetraxate (800 mg) or placebo were orally administered to five healthy males. Blood samples were taken before, and at 20, 40, 60, 90, 120, 180 and 240 min after administration, followed by the extracting procedure, and submitted to a highly sensitive enzyme immunoassay system for CGRP and substance P. Single administration of cetraxate caused significant increases in plasma CGRP concentration at 60–120 min compared with placebo. Cetraxate significantly increased plasma substance P levels at 40–90 min compared with placebo. In this study, we hypothesized that cetraxate might indirectly stimulate capsaicin-sensitive afferent nerves and increase mucosal blood flow, and that this may be a key mechanism underlying its gastroprotective action.
Losartan but not enalaprilat acutely reduces reperfusion ventricular tachyarrhythmias in hypertrophied rat hearts after low-flow ischaemia
Authors: Butz Silvia , Driamov Sergey , Remondino Andrea , Bellahcene Mohamed , Ziegler André , Zaugg Christian E , Beier Konstantin , Buser Peter T 
Published: April 2004

Abstract
Based on clinical and experimental studies, angiotensin II receptor blockers and angiotensin converting enzyme inhibitors have been proposed to exert acute anti-arrhythmic effects in heart failure patients. Therefore, the goal of this study was to assess acute anti-arrhythmic effects of losartan and enalaprilat in hypertrophied rat hearts during low-flow ischaemia and reperfusion. In dose-finding experiments in non-hypertrophied isolated perfused hearts, we performed dose-response curves of losartan and enalaprilat studying monophasic action potential duration at 90% repolarisation (MAPD90%) and ventricular fibrillation (VF) threshold. Subsequently, we determined the effects of losartan and enalaprilat (in therapeutically relevant concentrations) on ventricular tachyarrhythmias induced by low-flow ischaemia/reperfusion in hearts demonstrating left ventricular (LV) hypertrophy 70 days after aortic banding. We found that neither drug significantly affected MAPD90% (1 nm-1 mm) or VF threshold (1 μm losartan and 10 μm enalaprilat) in non-hypertrophied hearts. Similarly in hypertrophied hearts, neither drug significantly affected the incidence or the duration of ventricular tachyarrhythmias (ventricular tachycardia and VF) during low-flow ischaemia. However, 1 μm losartan significantly reduced the duration of ventricular tachyarrhythmias during reperfusion. In conclusion, neither losartan nor enalaprilat is acutely anti-arrhythmic in hypertrophied rat hearts during low-flow ischaemia. During reperfusion, however, losartan but not enalaprilat exerts acute anti-arrhythmic effects.
Influence of enhancers on the absorption and on the pharmacokinetics of cefodizime using in-vitro and in-vivo models
Authors: Mrestani Yahya , Bretschneider Beate , Neubert Reinhard H H , Härtl Albert , Brandsch Matthias 
Published: April 2004

Abstract
In the development of novel antibiotics, more and more compounds have been found that cannot be absorbed orally and, therefore, must be administered intravenously or intramuscularly. Because of the obvious drawbacks of drug delivery by injection, the development of alternatives with enhanced oral bioavailability has received much attention in pharmaceutical research. Cefodizime, a novel third-generation cephalosporin with significant advantages in the parenteral treatment of common infections, was used as a model drug. Cefodizime behaves as a highly hydrophilic compound, as shown from its extremely low partition coefficient. The effect of cationic absorption enhancers (hexadecyldimethyl-benzylammonium chloride, N-hexadecylpyridinium bromide, dodecyltrimethylammonium bromide and hexadecyltrimethylammonium bromide) on the lipophilicity of cefodizime was investigated by means of the n-octanol/water system. Results showed that the counter-ions had a positive influence on the solubility of cefodizime. These results on partitioning coefficients in the n-octanol/buffer system were confirmed using an in-vitro transport model with artificial and biological membranes (Caco-2-cells). Furthermore, the physiological compatibility of the absorption enhancers was investigated using the active d-glucose transport. The pharmacokinetic profile of cefodizime was evaluated in rabbits after intraduodenal administration with and without an absorption enhancer.
The lamin B receptor of Drosophila melanogaster
Authors: Wagner Nicole , Weber Daniela , Seitz Sabine , Krohne Georg 
Published: April 2004

The lamin B receptor (LBR) is an integral membrane protein of the inner nuclear membrane that has so far been characterized only in vertebrates. Here, we describe the Drosophila melanogaster protein encoded by the annotated gene CG17952 that is the putative ortholog to the vertebrate LBR. The Drosophila lamin B receptor (dLBR) has the following properties in common with the vertebrate LBR. First, structure predictions indicate that the 741 amino acid dLBR protein possesses a highly charged N-terminal domain of 307 amino acids followed by eight transmembrane segments in the C-terminal domain of the molecule. Second, immunolocalization and cell fractionation reveal that the dLBR is an integral membrane protein of the inner nuclear membrane. Third, dLBR can be shown by co-immunoprecipitations and in vitro binding assays to bind to the Drosophila B-type lamin Dm0. Fourth, the N-terminal domain of dLBR is sufficient for in vitro binding to sperm chromatin and lamin Dm0. In contrast to the human LBR, dLBR does not possess sterol C14 reductase activity when it is expressed in the Saccharomyces cerevisiae erg24 mutant, which lacks sterol C14 reductase activity. Our data raise the possibility that, during evolution, the enzymatic activity of this insect protein had been lost.To determine whether the dLBR is an essential protein, we depleted it by RNA interference in Drosophila embryos and in cultured S2 and Kc167 cells. There is no obvious effect on the nuclear architecture or viability of treated cells and embryos, whereas the depletion of Drosophila lamin Dm0 in cultured cells and embryos caused morphological alterations of nuclei, nuclear fragility and the arrest of embryonic development. We conclude that dLBR is not a limiting component of the nuclear architecture in Drosophila cells during the first 2 days of development.
Grammont inverted total shoulder arthroplasty in the treatment of glenohumeral osteoarthritis with massive rupture of the cuff
Authors: Sirveaux F. , Favard L. , Oudet D. , Huquet D. , Walch G. , Mole D. 
Published: April 2004

We reviewed 80 shoulders (77 patients) at a mean follow-up of 44 months after insertion of a Grammont inverted shoulder prosthesis. Three implants had failed and had been revised. The mean Constant score had increased from 22.6 points pre-operatively to 65.6 points at review. In 96% of these shoulders there was no or only minimal pain. The mean active forward elevation increased from 73° to 138°. The integrity of teres minor is essential for the recovery of external rotation and significantly influenced the Constant score. Five cases of aseptic loosening of the glenoid and seven of dissociation of the glenoid component were noted. This study confirms the promising early results obtained with the inverted prosthesis in the treatment of a cuff-tear arthropathy. It should be considered in the treatment of osteoarthritis with a massive tear of the cuff but should be reserved for elderly patients.
Long-term deterioration of joint evaluation scores
Authors: Ritter M. A. , Thong A.E. , Davis K.E. , Berend M. E. , Meding J. B. , Faris P. M. 
Published: April 2004

We investigated the long-term changes in the Harris Hip and Knee Society scores (HSS and KSS) to determine whether they result from overall functional decline rather than actual changes in the condition of the prosthesis. The HHS for 106 total hip arthroplasties with a minimum follow-up of ten years, no medical complications after operation and no evidence of radiological loosening, and the KSS for 264 total knee arthroplasties with a minimum follow-up of 12 years and no medical complications after operation or signs of radiographical loosening were evaluated. There were statistically significant drops in the functional scoring components of the joint evaluation systems despite no loosening of the prostheses or other significant medical complications. The HHS declined at an average of 0.67 points per year from between three and ten years after operation (p < 0.0001). Contributing to this were deterioration in gait and limp (p < 0.0004), the use of support aids (p < 0.0001), the distance walked (p < 0.0001) and the ability to climb stairs (p < 0.0455). The functional component of the KSS declined significantly at an average 0.88 points per year betwen the third and 12th years (p < 0.0001). There were significant declines in every component of the functional score including the distance walked (p < 0.0001), the ability to climb stairs (p < 0.0001) and the use of support aids (p < 0.0001). The knee score component of the KSS did not decline significantly (p < 0.9750). The combination of functional and pain scores within the HHS system leads to an inaccurate decline in the entire score. The decline of HHS and Knee Society functional scores in total joint arthroplasties, in the absence of implant-related problems, suggests that deterioration in the functional capacity of ageing patients is an important factor in longitudinal studies using these scoring systems.
The use of structural proximal femoral allografts in complex revision hip arthroplasty
Authors: Graham N. M. , Stockley I. 
Published: April 2004

Between April 1992 and November 1998 we used 34 massive proximal femoral allografts for femoral reconstruction at revision hip arthroplasty. Seven patients have died and two have been lost to follow-up. There were thus 25 grafts in 24 patients for review. The mean follow-up was 53 months (16 to 101). By the time of the review two patients had undergone a further revision for failure of the allograft. Another had required secondary plating and grafting at the graft-host junction for symptomatic nonunion. One had recurrence of deep sepsis and was being managed conservatively. Trochanteric union was considered to have occurred radiologically in 16 of the 25 grafts and union at the host-graft junction in 20. Resorption of the allograft was significant in only two hips. We recommend this technique in cases in which femoral bone loss has been catastrophic.
The posterior cruciate ligament during flexion of the normal knee
Authors: Nakagawa S. , Johal P. , Pinskerova V. , Komatsu T. , Sosna A. , Williams A. , Freeman M. A. R. 
Published: April 2004

The posterior cruciate ligament (PCL) was imaged by MRI throughout flexion in neutral tibial rotation in six cadaver knees, which were also dissected, and in 20 unloaded and 13 loaded living (squatting) knees. The appearance of the ligament was the same in all three groups. In extension the ligament is curved concave-forwards. It is straight, fully out-to-length and approaching vertical from 60° to 120°, and curves convex-forwards over the roof of the intercondylar notch in full flexion. Throughout flexion the length of the ligament does not change, but the separations of its attachments do. We conclude that the PCL is not loaded in the unloaded cadaver knee and therefore, since its appearance in all three groups is the same, that it is also unloaded in the living knee during flexion. The posterior fibres may be an exception in hyperextension, probably being loaded either because of posterior femoral lift-off or because of the forward curvature of the PCL. These conclusions relate only to everyday life: none may be drawn with regard to more strenuous activities such as sport or in trauma.
The influence on human osteoblasts in vitro of non-steroidal anti-inflammatory drugs which act on different cyclooxygenase enzymes
Authors: Evans C. E. , Butcher C. 
Published: April 2004

There is increasing evidence that non-steroidal anti-inflammatory drugs (NSAIDs) can adversely affect bone repair. We have, therefore, studied the in vitro effects of NSAIDs, which differentially inhibit cyclooxygenases (COX), the prostaglandin/thromboxane synthesising enzymes, on human osteoblasts. Indomethacin and the new nitric oxide (NO)-donating NSAIDs block the activity of both COX-1 and COX-2. Indomethacin and 5,5-dimethyl-3-(3 fluorophenyl)-4-(4 methylsulphonal) phenyl-2 (5H)-furanone (DFU) reduced osteoblast numbers in a dose-dependant manner and increased collagen synthesis and alkaline phosphatase activity. The reduction in osteoblast numbers was not caused by loss of adhesion and was reversible. Neither NSAID influenced DNA synthesis. There was no difference between the effects of indomethacin and DFU. NO-NSAIDs did not affect cell numbers. These results suggest that care should be taken when administering NSAIDs to patients with existing skeletal problems and that NO-NSAIDs may be safer.
Pattern of diabetic neuropathic arthropathy associated with the peripheral bone mineral density
Authors: Herbst S. A. , Jones K. B. , Saltzman C. L. 
Published: April 2004

The relationship between the bone mineral density (BMD) and Charcot arthropathy is unclear. Prospectively, 55 consecutive diabetic patients presenting with a Charcot arthropathy of the foot or ankle were classified as having a fracture, dislocation, or a combination fracture-dislocation pattern of initial destruction. In these groups we used dual-energy x-ray absorptiometry to compare the peripheral bone of the affected and unaffected limbs. The clinical data relating to diabetes and related major comorbidities and the site of the arthropathy (ankle, hindfoot, midfoot, forefoot) were also compared. There were 23 patients with a fracture pattern, 23 with a dislocation pattern, and nine with a combination. The age-adjusted odds ratio for developing a Charcot joint with a fracture pattern as opposed to a dislocation pattern in patients with osteopenia was 9.5 (95% confidence interval 2.4 to 37.4; p = 0.0014). Groups also differed as to the site of the arthropathy. Fracture patterns predominated at the ankle and forefoot whereas dislocations did so in the midfoot. Diabetic Charcot arthropathy of the foot and ankle differs according to the pattern of the initial destruction. The fracture pattern is associated with peripheral deficiency of BMD. The dislocation pattern is associated with a normal BMD.