bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacological actions of Cordyceps, a prized folk medicine
Authors: Ng T B , Wang H X 
Published: November 2005

Abstract
Cordyceps species, including C. sinensis, C. militaris, C. pruinosa and C. ophioglossoides, are prized traditional medicinal materials. The aim of this article is to review the chemical constituents and pharmacological actions of Cordyceps species. The chemical constituents include cordycepin (3′-deoxyadenosine) and its derivatives, ergosterol, polysaccharides, a glycoprotein and peptides containing α-aminoisobutyric acid. They include anti-tumour, anti-metastatic, immunomodulatory, antioxidant, anti-inflammatory, insecticidal, antimicrobial, hypolipidaemic, hypoglycaemic, anti-ageing, neuroprotective and renoprotective effects. Polysaccharide accounts for the anti-inflammatory, antioxidant, anti-tumour, anti-metastatic, immunomodulatory, hypoglycaemic, steroidogenic and hypolipidaemic effects. Cordycepin contributes to the anti-tumour, insecticidal and antibacterial activity. Ergosterol exhibits anti-tumour and immunomodulatory activity. A DNase has been characterized.
Controlled release tamsulosin hydrochloride from alginate beads with waxy materials
Authors: Kim Min-Soo , Park Gyeong-Deuk , Jun Seoung-Wook , Lee Sibeum , Park Jeong-Sook , Hwang Sung-Joo 
Published: November 2005

Abstract
The objective of this study was to develop oral controlled release delivery systems for tamsulosin hydrochloride (TSH) using alginate beads with various waxy materials, such as Compritol 888 ATO, Precirol ATO 5 and Gelucires. The beads were prepared from sodium alginate—waxy material—TSH slurry dropped onto calcium chloride to form spherical beads. The effects of the addition of various waxy materials to alginate beads on the drug encapsulation efficiency, bead size and morphology were investigated. The drug encapsulation efficiency significantly increased with the addition of waxy materials. The TSH-loaded alginate beads with and without waxy materials were almost spherical particles with an average diameter of 1.44 and 1.22mm, respectively. In dissolution study, the TSH-loaded alginate beads with waxy materials exhibited controlled release behaviour over a 6-h period, while beads without waxy materials showed release of 100% TSH within 2h. These results may be attributed to the formation of a more rigid alginate matrix structure due to incorporated waxy materials. From the Dunnett's t-test and the f2 factor, the release of TSH from alginate beads, a similar dissolution pattern to that of the marketed product (Harunal capsules) could be achieved by adding Gelucire 50/13 into TSH-loaded alginate beads. From these results, oral controlled release of TSH could be achieved with loading in alginate beads with waxy materials, such as Compritol 888 ATO, Precirol ATO 5 and Gelucires.
Cefuroxime axetil solid dispersions prepared using solution enhanced dispersion by supercritical fluids
Authors: Jun Seoung Wook , Kim Min-Soo , Jo Guk Hyun , Lee Sibeum , Woo Jong Soo , Park Jeong-Sook , Hwang Sung-Joo 
Published: November 2005

Abstract
Cefuroxime axetil (CA) solid dispersions with HPMC 2910/PVP K-30 were prepared using solution enhanced dispersion by supercritical fluids (SEDS) in an effort to increase the dissolution rate of poorly water-soluble drugs. Their physicochemical properties in solid state were characterized by differential scanning calorimeter (DSC), powder X-ray diffraction (PXRD), Fourier transform infrared spectrometry (FT-IR) and scanning electron microscopy. No endothermic and characteristic diffraction peaks corresponding to CA were observed for the solid dispersions in DSC and PXRD. FTIR analysis demonstrated the presence of intermolecular hydrogen bonds between CA and HPMC 2910/PVP K-30 in solid dispersions, resulting in the formation of amorphous or non-crystalline CA. Dissolution studies indicated that the dissolution rates were remarkably increased in solid dispersions compared with those in the physical mixture and drug alone. In conclusion, an amorphous or non-crystalline CA solid dispersion prepared using SEDS could be very useful for the formulation of solid dosage forms.
Clinical pharmacokinetics of the cyclooxygenase inhibiting nitric oxide donator (CINOD) AZD3582
Authors: Fagerholm Urban , Björnsson Marcus A 
Published: November 2005

AbstractThe clinical pharmacokinetics of the COX-inhibiting nitric oxide donator (CINOD) AZD3582 and its metabolites, including naproxen, nitric oxide and nitrate, are summarized. AZD3582 has low aqueous solubility, moderate and passive intestinal permeability and is degraded by intestinal esterases. Its oral bioavailability (F) appears to be maximally a few per cent, and increases by several-fold after food intake. Ninety-four per cent or more of an AZD3582 dose is absorbed, of which at least 9–20% appears to be taken up as intact substance. AZD3582 has a predicted plasma protein binding degree of ∼ 0.1%, a half-life (t½) of 3 to 10 h and does not accumulate after repeated once- and twice-daily dosing. In patients AZD3582 does not provide a significantly better gastrointestinal (GI) side-effect profile than the highly permeable and locally irritating naproxen. Possible reasons for this include considerable GI uptake as naproxen, limited duration and extent of nitric oxide donation in the GI mucosa and the circulation, tolerance development (involving auto-inhibition of nitric oxide catalysing enzymes) and mucosal damage caused by nitric oxide. Blood pressure data suggest that nitric oxide is mainly donated within 3h. The uptake of naproxen is slightly slower and lower (≥ 94% relative GI uptake and 80–85% relative F) after AZD3582 administration compared with naproxen dosing. The naproxen t½ and trough steady-state concentrations after AZD3582 and naproxen dosing are similar. The average systemic nitrate exposure is approximately doubled after dosing of 375 to 750 mg AZD3582 twice daily.
Size-dependent disposition of nanoparticles and microparticles following subconjunctival administration
Authors: Amrite Aniruddha C , Kompella Uday B 
Published: November 2005

Abstract
The purpose of this study was to determine the retention and ocular distribution of subconjunctivally administered nanoparticles and microparticles. Fluorescent polystyrene particles (carboxylate modified, negatively charged) of various sizes (20 nm, 200 nm and 2 μm; Fluospheres, dose 400 μg) were administered to male Sprague-Dawley rats by subconjunctival injection under anaesthesia. The disposition of the particles in the periocular and ocular tissues was studied for up to 60 days by quantifying the particle amounts using liquid extraction followed by spectrofluorimetric analysis. The effect of dose on the particle disposition was investigated with a 40-μg dose of the particles. The effect of an increase in surface hydrophobicity was evaluated for the 20 and 200 nm particles at 1 day post administration. Following periocular administration, penetration into the ocular tissues was negligible for the carboxylate-modified microparticles as well as nanoparticles. Almost the entire dose of the 200 nm and 2 μm particles was retained in the periocular tissue at 60 days post-administration. The 20 nm particles disappeared rapidly from the periocular tissue with 15 and 8% of administered dose remaining after 1 and 7 days, respectively. The 20 nm particles could not be detected in the periocular tissue at 60-days post-administration. An increase in the surface hydrophobicity did not affect the periocular retention of 200 nm particles but elevated that of the 20 nm particles, at the end of day 1. It was concluded that subconjunctivally administered 200 nm and larger particles can be almost completely retained at the site of administration for at least two months. Periocular administration of particulate systems of this size would likely be useful as sustained drug delivery systems.
Sulfasalazine transport in in-vitro, ex-vivo and in-vivo absorption models: contribution of efflux carriers and their modulation by co-administration of synthetic nature-identical fruit extracts
Authors: Mols Raf , Deferme Sven , Augustijns Patrick 
Published: November 2005

AbstractSulfasalazine is characterised by low oral bioavailability. In this study, its intestinal transport characteristics were studied in an in-vitro, ex-vivo and in-situ system. The absorptive transport of sulfasalazine across Caco-2 monolayers appeared to be lower than the secretory transport (Papp-abs = 0.21 ± 0.02 times 10−6 cm s−1 and Papp-secr = 2.97 ± 0.30 times 10−6 cm s−1, respectively). This polarity in transport of sulfasalazine was not mediated by P-glycoprotein (P-gp), as inclusion of verapamil (100 μm) did not have any effect on the transport polarity of sulfasalazine. However, inclusion of the multidrug resistance-associated protein (MRP) inhibitors benzbromarone (50 μm) and sulfinpyrazone (1 mm), and the glutathione-depleting agent chlorodinitrobenzene (100 μm), resulted in an increased absorptive transport of sulfasalazine in the Caco-2 system (Papp-abs = 0.64 ± 0.02, 0.51 ± 0.04 and 0.60 ± 0.03 times 10−6 cm s−1, respectively). The interference of carriers implies that, during absorption, interactions with food components may occur at the level of this carrier. Therefore, the effect of food extracts was studied in a parallel set of experiments. For two standardized nature-identical fruit extracts (pineapple and apricot extract) a concentration-dependent absorption-enhancing effect could be observed in the Caco-2 system. The functional expression of similar carriers was also demonstrated in rat ileum in the Ussing chamber system. Interaction studies with fruit extracts in the Ussing chamber system, as well as in the in-situ intestinal perfusion study, revealed a 2- to 4-fold increase in the absorptive transport of sulfasalazine. These results indicate that food components in the intestinal lumen can have a significant impact on the intestinal absorption characteristics of sulfasalazine by modulating the biochemical barrier function of the intestinal mucosa.
Antidiabetic effect of a new peptide from Squalus mitsukurii liver (S-8300) in streptozocin-induced diabetic mice
Authors: Huang Fengjie , Wu Wutong 
Published: November 2005

Abstract
We have evaluated the antidiabetic effect of S-8300 (a peptide extracted from shark liver (Squalus mitsukurii)) in streptozocin (streptozotocin)-diabetic mice. Diabetes was induced by a single intravenous injection of streptozocin (150 mg kg−1). The effects of S-8300 (3 or 10 mg kg−1) on diabetic mice were investigated by observing the changes in the levels of fasting plasma glucose, glycosylated haemoglobin, hepatic glycogen, triglycerides, cholesterol, free fatty acid, superoxide dismutase, and malondialdehyde. Body weight, kidney weight and the degree of injured β-cells in pancreatic islets were recorded also. Diabetic mice treated with S-8300 showed a significant decrease in the levels of fasting plasma glucose, glycosylated haemoglobin, triglycerides, cholesterol, free fatty acid in plasma and malondialdehyde in tissues. The animals showed a significant increase in the content of hepatic glycogen and the activity of superoxide dismutase. Treatment with S-8300 attenuated the degree of injured β-cells in the pancreatic islets. The effect of S-8300 was similar to that of glibenclamide (5 mg kg−1).
Cytoprotective mechanism of baicalin against endothelial cell damage by peroxynitrite
Authors: Kim Dae Hyun , Chung Hae Young , Cho Ki Ho , Moon Sang Kwan , Kim Young Suk , Kim Dong Hyun , Choi Jae Sue 
Published: November 2005

Abstract
To evaluate the mechanism responsible for the cytoprotective effects of baicalin, an antioxidant flavonoid isolated from Scutellaria baicalensis, we investigated its effects against peroxynitrite (ONOO−)-induced endothelial cell (EC) damage. Baicalin showed efficient antioxidative actions by its ability to scavenge ONOO− and inhibit ONOO−-mediated nitrotyrosine formation in vitro. Using an EC (YPEN-1) culture system, baicalin exhibited cytoprotective effects against cell death by ONOO− that was induced exogenously with tert-butyl hydroperoxide (t-BHP) in the YPEN-1 model. Baicalin was also found to reduce the intracellular precursors of ONOO−, NO˙ and O2− in the t-BHP-treated ECs. Evidence from Western blotting further revealed down-regulated expressions of iNOS and COX-2, endogenous sources of NO˙ and O2− by baicalin treatment. In addition, pre-incubation of baicalin with EC suppressed t-BHP-induced nuclear factor kappa-B binding activity as determined by the transfection assay and Western blot analysis, further indicating baicalin's inhibition of iNOS and COX-2 expression. Based on the present data, we propose that baicalin scavenges ONOO− and protects cells against injury. Based on these data, it was concluded that baicalin is potentially a useful antioxidant against ONOO− and NO˙ and an inhibitor of iNOS and COX-2.
Apoptotic potential of sesquiterpene lactone ergolide through the inhibition of NF-κB signaling pathway
Authors: Song Yong Jin , Lee Dae Young , Kang Dong-Won , Kim Yong Kee , Kim Su-Nam , Lee Kang Ro , Lee Hyang Woo , Han Jeung-Whan , Lee Hoi Young 
Published: November 2005

Abstract
Treatment with ergolide, a sesquiterpene lactone from Inula britannica var chinensis, caused the induction of apoptosis in Jurkat T cells, which was confirmed by DNA fragmentation, caspase-3 activation and cleavage of poly(ADP-ribose) polymerase in response to ergolide. Furthermore, mitochondrial dysfunction appeared to be associated with ergolide-induced apoptosis, because Bax translocation and cytochrome c release were stimulated by ergolide. In parallel, the nuclear factor-κB (NF-κB) signaling pathway was significantly inhibited by ergolide, which was accompanied by down-regulation of cell survival molecules, such as X-chromosome-linked inhibitor of apoptosis and Bcl-2. In addition, the JNK signaling pathway was involved in ergolide-induced apoptosis. Collectively, our results identified a new mechanism for the anti-cancer property of ergolide, attributable to the induction of apoptosis through down-regulation of cell survival signal molecules resulting from inhibition of the NF-κB signaling pathway.
The role of endothelin receptor antagonism in collar-induced intimal thickening and vascular reactivity changes in rabbits
Authors: Reel Buket , Sozer Gonen Ozsarlak , Turkseven Saadet , Kerry Zeliha , Ozkal Sermin , Ozer Erdener , Islekel Huray , Oktay Gulgun , Tanriverdi Serpil 
Published: November 2005

AbstractIntimal thickening, due to smooth muscle cell migration and proliferation, is considered to be one of the major components of vascular proliferative disorders such as atherosclerosis and restenosis. One experimental model, resulting in intimal thickening in the rabbit, involves placing a silicon collar around the carotid artery, and is used in this study. Endothelin is known to act as a strong mitogen and to stimulate smooth muscle cell proliferation and migration. We investigated the contribution of endothelin to the development of collar-induced intimal thickening and the effects of TAK-044, (5mg kg−1 daily, s.c.), a non-selective ETA/ETB receptor antagonist, on intimal thickening and vascular reactivity changes in the collared rabbit carotid artery. Endothelin levels and the intimal cross-sectional area, as well as the ratio of intimal area to media (index), increased significantly in collared arteries as compared with those in sham-operated arteries. TAK-044 significantly inhibited intimal thickening and also decreased the index without affecting increased endothelin levels in collared arteries. Vascular reactivity changes in response to collaring produced predictable effects, such as decreased contractile responses to vasoconstrictor agents and increased sensitivity to serotonin (5-hydroxytrypt-amine, 5-HT). In terms of contractile responses in this model, TAK-044, in particular, did not affect collar-induced vascular reactivity changes. These results suggest that endothelin may be involved in the pathogenesis of collar-induced intimal thickening. As an endothelin receptor antagonist, TAK-044 may potentially be beneficial in the treatment of atherosclerosis.
The phosphodiesterase 4 inhibitor AWD 12–281 is active in a new guinea-pig model of allergic skin inflammation predictive of human skin penetration and suppresses both Th1 and Th2 cytokines in mice
Authors: Hoppmann Joachim , Galetzka Christin , Höfgen Norbert , Rundfeldt Chris , Bämer Wolfgang , Kietzmann Manfred 
Published: November 2005

AbstractThe selective phosphodiesterase 4 (PDE4) inhibitor AWD 12–281 is structurally optimized for topical administration. It has potent effects in models of lung inflammation if administered as a dry powder inhalation. It has also demonstrated its anti-inflammatory property in a mouse model of cutaneous inflammation after topical administration. The aim of this study was to evaluate whether AWD 12–281 may be capable of penetrating human skin. Therefore a new guinea-pig model of allergic skin inflammation had to be developed. In ovalbumin-sensitized guinea-pigs, intracutaneous administration of ovalbumin results in a rapid development of allergic skin wheals. Topically administered AWD 12–281 was capable of reducing the development of wheals, indicating that this compound can penetrate the stratum corneum of guinea-pig skin as a predictor of human skin penetration. A secondary aim was the evaluation of a T cell subtype preference of AWD 12–281 since PDE4 inhibitors are said to preferentially inhibit Th2-type cytokines. Therefore, the effects of AWD 12–281 on a broad spectrum of Th1- and Th2-type cytokines were studied in tissue homogenates after allergen challenge in sensitized mice and in supernatants of anti CD3/anti-CD28-stimulated peripheral blood mononuclear cells (PBMCs). In both models, AWD 12–281 suppressed both T cell subtype cytokines indicating a broad spectrum activity of AWD 12–281. A further issue was to determine the duration of action and the concentration-response relationship of the topical activity of AWD 12–281 using a model of acute local inflammation — the arachidonic-acid-induced mouse ear oedema. The compound exhibited a dose-dependent effect with a minimally effective concentration of 0.3%; after repeated administration the minimally effective concentration was found to be 0.03%. A single administration of a 3% solution resulted in significant suppression of inflammation even 48 h after treatment. In conclusion, our results indicate that AWD 12–281 is a very promising drug candidate not only for the treatment of lung inflammation using inhalative administration but also for the treatment of atopic dermatitis.
Preparation and stereochemical integrity of certain thioesters of 2-arylpropionic acids and related compounds
Authors: Hanrahan Patrick E , Moynihan Humphrey A 
Published: November 2005

Abstract
2-Arylpropionate thioesters 5, 6a/6b and 7a/7b, 2-aryloxypropionate thioesters 8a/8b and 2-alkoxy-2-arylacetate thioesters 9a/9b were prepared from thiol 4 and the corresponding carboxylic acids. Thioesters 6a/6b, 7a/7b, 8a/8b and 9a/9b were monitored for evidence of inter-conversion between epimers in acetonitrile solvent at 40°C, by optical activity in the cases of 6a/6b and 7a/7b, and by 1H NMR spectroscopy in the cases of 8a/8b and 9a/9b. Only in the case of thioesters 9a/9b was significant inter-conversion between epimers observed.
Gastroprotection and effect of the simultaneous administration of Cuachalalate (Amphipterygium adstringens) on the pharmacokinetics and anti-inflammatory activity of diclofenac in rats
Authors: Navarrete Andrés , Sánchez-Mendoza María Elena , Arrieta Jesús , Cruz-Antonio Leticia , Oliva Iván , Castañeda-Hernández Gilberto 
Published: November 2005

Abstract
This work aimed to study the effect of Cuachalalate methanol extract (CME) on the anti-inflammatory activity and pharmacokinetics of diclofenac sodium, a frequently prescribed non-steroidal antiinflammatory drug (NSAID). The gastroprotective effect of CME on the gastric injury induced by diclofenac was studied in rats. CME showed a gastroprotective effect of 15.7% at 1 mg kg−1 and 72.5% at dose of 300 mg kg−1. Omeprazole, used as anti-ulcer reference drug, showed gastroprotective effects of 50–89.7% at doses tested (1–30 mg kg−1). The value of the 50% effective dose for the anti-inflammatory effect of diclofenac sodium (ED50 = 1.14 ± 0.23 mg kg−1) using carrageenaninduced rat paw oedema model, was not modified by the concomitant administration of 30 or 100 mg kg−1 of CME. The effect of CME (30, 100 and 300 mg kg−1, p.o.) on the pharmacokinetics of diclofenac sodium was studied. It was observed that the simultaneous administration of diclofenac sodium and 300 mg kg−1 of CME decreased significantly the values of Cmax (7.08 ± 1.42 μg mL−1) and AUC (12.67 ± 2.97 μg h mL−1), but not the value of tmax (0.13 (0.1–0.25) h) obtained with the administration of diclofenac alone. The simultaneous administration of 30 or 100 mg kg−1 of CME did not modify the pharmacokinetic parameters of diclofenac. The experimental findings in rats suggest that CME at doses lower than 100 mg kg−1 protects the gastric mucosa from the damage induced by diclofenac sodium without altering either the anti-inflammatory activity or the pharmacokinetics of this NSAID.
Protective effect of Hachimi-jio-gan against renal failure in a subtotal nephrectomy rat model
Authors: Yamabe Noriko , Yokozawa Takako , Kim Hyun Young , Cho Eun Ju 
Published: November 2005

Abstract
The protective effect of Hachimi-jio-gan extract against chronic renal failure in a subtotal nephrectomy rat model was investigated. The level of serum urea nitrogen by nephrectomy was increased over 15 weeks, but the administration of Hachimi-jio-gan at 50 and 200 mg led to the decrease. In addition, the levels of creatinine (Cr), urinary methylguanidine (MG) and MG/Cr were increased, whereas Cr clearance dramatically decreased in nephrectomized rats. However, oral administration of Hachimi-jio-gan extract prevented the elevation of these uremic toxins in serum and urine, and the production of hydroxyl radical. Moreover, nephrectomy led to a significant decline in superoxide dismutase (SOD) and catalase activities, but increased glutathione peroxidase activity compared with normal levels, indicating an abnormal antioxidative system. The increased activity of both SOD and catalase by the oral administration of Hachimi-jio-gan suggested that these enzymes are associated with the protective role of Hachimi-jio-gan extract against oxidative stress by nephrectomy. Moreover, the decrease in serum albumin in nephrectomized control rats was increased and proteinuria was ameliorated by the administration of Hachimi-jio-gan with improved glomerular hyalinosis, interstitial fibrosis and inflammation, suggesting the beneficial effect of Hachimi-jio-gan to prevent glomerular sclerosis and progressive renal fibrosis. This study suggests that Hachimi-jio-gan plays a protective role in the progression of chronic renal failure through the decline in uremic toxins, elevation of antioxidative enzyme activity such as SOD and catalase, and amelioration of histopathological lesions in the kidney.