bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene therapy used for tissue engineering applications
Authors: Heyde Mieke , Partridge Kris A , Oreffo Richard O C , Howdle Steven M , Shakesheff Kevin M , Garnett Martin C 
Published: February 2007

Abstract
This review highlights the advances at the interface between tissue engineering and gene therapy. There are a large number of reports on gene therapy in tissue engineering, and these cover a huge range of different engineered tissues, different vectors, scaffolds and methodology. The review considers separately in-vitro and in-vivo gene transfer methods. The in-vivo gene transfer method is described first, using either viral or non-viral vectors to repair various tissues with and without the use of scaffolds. The use of a scaffold can overcome some of the challenges associated with delivery by direct injection. The ex-vivo method is described in the second half of the review. Attempts have been made to use this therapy for bone, cartilage, wound, urothelial, nerve tissue regeneration and for treating diabetes using viral or non-viral vectors. Again porous polymers can be used as scaffolds for cell transplantation. There are as yet few comparisons between these many different variables to show which is the best for any particular application. With few exceptions, all of the results were positive in showing some gene expression and some consequent effect on tissue growth and remodelling. Some of the principal advantages and disadvantages of various methods are discussed.
Formulation, preparation and evaluation of flunarizine-loaded lipid microspheres
Authors: Wang Yan Jiao , Wang Juan , Zhang Hong Yao , He Hai Bing , Tang Xing 
Published: February 2007

Abstract
The aim of this study was to investigate the feasibility of preparing flunarizine-loaded lipid microspheres. Lipid microspheres (LMs) are excellent drug carriers for drug delivery systems (DDS) and are relatively stable and easily mass-produced. They have no particular adverse effects. LMs have been widely studied as drug carriers for water-soluble drugs, lipid-soluble drugs and inadequately soluble (in water or in lipid) drugs, in that they have a lipid layer, a water layer and an emulsifier layer. Flunarizine (FZ), a poorly water-soluble drug, was incorporated in lipid microspheres to reduce side effects by avoiding the use of supplementary agents, compared with solution injection. After investigation, the final formulation was as follows: 10% oil phase (long-chain triglyceride (LCT); medium-chain fatty acid (MCT) = 50:50); 1.2% egg lecithin; 0.2% Tween-80; 2.5% glycerin; 0.3% dl-α-tocopherol; 0.02% EDTA; 0.03% sodium oleate; 0.1% FZ and double-distilled water to give a total volume of 100 mL. Homogenization was the main method of preparation and the best conditions were a temperature of 40°C, a pressure of 700–800 bar and a suitable cycle frequency of about 10. The particle size distribution, zeta-potential and entrapment efficacy were found to be 198.7 ± 54.0 nm, −26.4mV and 96.2%, respectively. Its concentration in the preparation was 1.0mg mL−1. The lipid microspheres were stable during storage at 4°C, 25°C and 37°C for 3 months. Pharmacokinetic studies were performed in rats using a dose of 1.0 mg kg−1. The pharmacokinetic parameters were as follows: AUC0-t 6.13 μg h mL−1, t½ 5.32 h and Ke 0.16 Lh−1. The preparation data fitted a two-compartment model estimated by using 3p87 analysis software. From the observed data, FZ encapsulated in LMs did not significantly alter the pharmacokinetic characteristic compared with the FZ solution injection and did not produce a delayed release effect, when it was released in-vivo in rats. However, the availability of the drug was increased. These results suggested that this LM system is a promising option for the preparation of the liquid form of FZ for intravenous administration.
Compression coated systems for colonic delivery of 5-fluorouracil
Authors: Sinha V R , Singh Asmita , Singh Sanjay , Bhinge J R 
Published: February 2007

Abstract
Compression coating is one of the approaches for delaying the release of drugs. The aim of this study was to develop colon-specific compression coated systems of 5-fluorouracil (5-FU) for the treatment of colorectal cancer using xanthan gum, boswellia gum and hydroxypropyl methylcellulose (HPMC) as the coating materials. Core tablets containing 50 mg of 5-FU were prepared by direct compression. The coating of the core tablets was done using different coat weights (230, 250, 275 and 300 mg) and different ratios (1:2, 2:1, 1:3, 1:7 and 3:4) of boswellia gum and xanthan gum and different ratios (1:1, 1:2, 2:1, and 2:3) of boswellia gum and HPMC. In-vitro release studies were carried out using simulated gastric and intestinal fluids, with and without rat caecal contents. Among the different ratios used for coating with boswellia:xanthan gum combination, ratio 1:3 gave the best release profile with the lowest coating weights of 230 mg (7.47 ± 1.56% in initial 5 h). Further increase in the coat weights to 250, 275 and 300 mg led to drug release of 5.63 ± 0.53%, 5.09 ± 1.56% and 4.57 ± 0.88%, respectively, in the initial 5 h and 96.90 ± 0.66%, 85.05 ± 1.01% and 80.22 ± 0.35%, respectively, in 24h. When coating was carried out using different ratios of the combination boswellia gum and HPMC, the ratio 2:3 gave the best results among the initial trial batches (7.80 ± 0.57% in 5 h). Increasing the coat weights to 250, 275 and 300 mg led to drug release of 6.5 ± 0.27%, 3.70 ± 2.3% and 2.99 ± 0.72%, respectively, in the initial 5h and 96.90 ± 0.66%, 85.05 ± 1.01% and 80.22 ± 0.35%, respectively, in 24h. In-vitro studies were further carried out in the presence of 2% w/v rat caecal contents, which led to complete release of the drug from the tablets. Therefore, this study lays a basis for use of compression coating of 5-FU as a tool for delaying the release of the drug, which ensures better clinical management of the disease.
Hypromellose films for the delivery of growth factors for wound healing
Authors: Braund Rhiannon , Tucker Ian G , Medlicott Natalie J 
Published: February 2007

Abstract
Hypromellose was investigated as a carrier for extending topical growth factor delivery to wounds. Films of hypromellose (E4M, K4M and E10M) containing a model protein horseradish peroxidase (1 % w/w HRP, MW 40 000) were cast from aqueous solutions and dried at 37°C. In-vitro release was determined using Franz-type diffusion cells and films were mounted directly into the Franz cell or cast onto a wound dressing (Melolin) backing. There was an initial burst release then an extended release over 5 h. The Melolin backing significantly reduced the burst but not the extended release rates (P &lt; 0.05). Release of HRP was also determined from 7% w/v hypromellose gels and was significantly lower for E10M than E4M, suggesting that, once hydrated, the E10M hypromellose provides the greatest resistance to HRP release. The release profile of basic fibroblast growth factor from Melolin-backed films made from E4M hypromellose was not significantly different at any time point to that of HRP release from the same formulation. Hypromellose may be incorporated into a wound dressing such as Melolin to provide a prolonged release of an incorporated protein active.
Characterisation of blends of paracetamol and citric acid
Authors: Hoppu Pekka , Jouppila Kirsi , Rantanen Jukka , Schantz Staffan , Juppo Anne M 
Published: February 2007

Abstract
The purpose of this study was to characterise physically stable amorphous blends that were sticky (low glass transition temperature) in ambient conditions. The effects of composition, melting time and melting temperature were evaluated with respect to physical and chemical property. Citric acid anhydrate and paracetamol were melt-quenched as binary mixtures and as pure materials. Bulk samples were characterised by differential scanning calorimetry, X-ray powder diffractometry, and Raman and Fourier transform infrared spectroscopy. The composition and the sample exposure to moisture affected significantly the physical stability of samples. The extreme melting conditions, coupled with long exposure to heat and a high melting temperature, lowered the overall crystallisation rate. Paracetamol had a stronger tendency to crystallise from the blends than did citric acid. The 50:50% (w/w) blend was physically stable for at least 27 weeks in dry conditions and was partly crystalline after 4 weeks of storage at a relative humidity of 43%. The result of the physical stability of blends is discussed in terms of hydrogen bonding interaction between paracetamol and citric acid and in relation to degradation products formed in a mixing state.
Investigation of low levels of plasma valproic acid concentration following simultaneous administration of sodium valproate and rizatriptan benzoate
Authors: Hokama Nobuo , Hobara Norio , Kameya Hiromasa , Ohshiro Susumu , Hobara Narumi , Sakanashi Matao 
Published: February 2007

AbstractDrug interaction between rizatriptan benzoate, an anti-migraine agent, and sodium valproate (VPA-Na), an anticonvulsant, was studied in rats. When rizatriptan benzoate was administered orally immediately after VPA-Na oral administration, the pharmacokinetic parameters, such as plasma valproic acid (VPA) and area under the plasma concentration-time curve up to 3 h (AUC0–3), were significantly decreased compared with those in the control group. However, when rizatriptan benzoate was administered intraperitoneally immediately after VPA-Na orally, these parameters were not changed. In addition, when benzoic acid was administered orally immediately after VPA-Na orally, these were significantly lower compared with the control values. Therefore, it might be possible that VPA transport by monocarboxylate transporter was competitively inhibited by rizatriptan benzoate and thus absorption of VPA was decreased.
Pharmacokinetics and distribution of clioquinol in golden hamsters
Authors: Bondiolotti Gianpietro , Sala Mariaelvina , Pollera Claudia , Gervasoni Marco , Puricelli Maria , Ponti Wilma , Bareggi Silvio R 
Published: February 2007

Abstract
Clioquinol (5-chloro-7-iodo-8-quinolinol) is a zinc and copper chelator that can dissolve amyloid deposits and may be beneficial in Alzheimer's disease. Prion diseases are also degenerative CNS disorders characterised by amyloid deposits. The pharmacokinetics and tissue distribution of drugs active against prions may clarify their targets of action. We describe the harmacokinetics of clioquinol in hamster plasma, spleen and brain after single and repeated oral or intraperitoneal administration (50 mg kg−1), as well as after administration with the diet. A single intraperitoneal administration led to peak plasma clioquinol concentrations after 15 min (Tmax), followed by a decay with an apparent half-life of 2.20 ± 1.1 h. After oral administration, Tmax was reached after 30 min and was followed by a similar process of decay; the AUC0-last was 16% that recorded after intraperitoneal administration. The Cmax and AUC values in spleen after a single administration were about 65% (i.p.) and 25% (p.o.) those observed in blood; those in liver were 35% (p.o.) those observed in blood and those in brain were 20% (i.p.) and 10% (p.o.) those observed in plasma. After repeated oral doses, the plasma, brain and spleen concentrations were similar to those observed at the same times after a single dose. One hour after intraperitoneal dosing, clioquinol was also found in the ventricular CSF. Clioquinol was also given with the diet; its morning and afternoon concentrations were similar, and matched those after oral administration. No toxicity was found after chronic administration. Our results indicate that clioquinol, after oral administration with the diet, reaches concentrations in brain and peripheral tissues (particularly spleen) that can be considered effective in preventing prion accumulation, but are at least ten times lower than those likely to cause toxicity.
Intestinal efflux transport kinetics of green tea catechins in Caco-2 monolayer model
Authors: Chan K Y , Zhang Li , Zuo Zhong 
Published: February 2007

AbstractThe bioavailability of green tea catechins (GTCs), including epigallocatechin gallate (EGCG), epigal-locatechin (EGC), epicatechin gallate (ECG) and epicatechin (EC) is low in both animals and humans. The contribution of intestinal efflux to this low bioavailability has been suggested by previous studies. The objective of the present study was to investigate the kinetics of efflux transport of the four major GTCs in Caco-2 cell lines, to provide comparison on the efflux transport between each GTC. The basal-to-apical transport of each GTC at concentrations ranging from 15 to 265 μM was examined using the Caco-2 cell monolayer model. Transported amount of GTC was measured by high-performance liquid chromatography with electrochemical detection. Kinetic parameters, Vmax, Km and Vmax/Km were determined and compared among the four studied GTCs. The extent of basal-to-apical transport was, in descending order, EC &gt; EGC &gt; ECG ≅ EGCG. Kinetic studies indicated that active and saturable efflux transport of EC took place in Caco-2 cells, with a Km of 131 μM, a Vmax of 0.0249 nmol min cm−2 and an intrinsic clearance (Vmax/Km) of 0.19 μL min cm−2. No saturation could be observed for the efflux transport of EGC, ECG and EGCG even at concentrations up to about 200 μM, which may be due to their low affinity towards the transporters at the concentration range studied. In conclusion, the extent of efflux transport of GTCs in Caco-2 cells was, in descending order, EC &gt; EGC &gt; ECG ≅ EGCG, which may reflect the order of elimination occurring in the intestine. The kinetic studies showed the importance of efflux transporters in basal-to-apical transport of EC and suggests their role in the limited oral bioavailability of EC.
Bioavailability and tissular distribution of docetaxel, a P-glycoprotein substrate, are modified by interferon-α in rats
Authors: Reguiga Makrem Ben , Bonhomme-Faivre Laurence , Farinotti Robert 
Published: February 2007

Abstract
Interferon-α (IFN-α) inhibits intestinal P-glycoprotein (P-gp) expression in rats. In the present study, the effects of repeated pre-treatment with recombinant human INF-α (rhIFN-α) on oral and intravenous pharmacokinetics of a P-gp substrate, docetaxel (DTX; Taxotere) were investigated in a rat model. The bioavailability and distribution in different organs were also studied. Sprague-Dawley rats were subcutaneously pre-treated with either rhIFN-α for 8 days (4MIUkg−1, once daily) or with pegylated-IFN-α (ViraferonPeg; 60 μg kg−1, Days 1, 4 and 7). The rats were then distributed into subgroups (n = 5–6) according to the pre-treatment type, and received one dose of [14C]DTX (20 mg kg−1) either orally or intravenously. Pharmacokinetics studies were then performed over 240 min, at the end of which tissues (intestine, liver, kidneys, lung, heart and brain) were immediately removed for radioactivity quantitation. Non-pegylated and pegylated IFN-αboth increased DTX oral bioavailability parameters: Cmax (17.0 ± 4.0 μgL−1 (P &lt; 0.02) and 18 ± 5.5 μg L−1 (P &lt; 0.05), respectively, vs 7.4 ± 2.5 μ g L−1 for the control) and AUC (0.036 ± 0.010 μg h mL−1 (P &lt; 0.01) and 0.033 ± 0.009 μgh mL−1(P &lt; 0.01), respectively, versus 0.012 ± 0.004 μghmL−1 for the control). IFN-α also delayed DTX absorption from 60 min in controls to about 95 min and 80 min in non-pegylated and pegylated treated animals, respectively. However, IFN-αdid not affect intravenous DTX pharmacokinetics and it had a limited effect on tissue distribution at 240 min. [14C]DTX was decreased in intestine and enhanced in brain in both pre-treated groups. rhIFN-α modified the P-gp-dependent pharmacokinetics of DTX, limited its intestinal efflux and markedly enhanced its oral bioavailability.
Measurements of oxidative stress status and antioxidant activity in chronic leukaemia patients
Authors: Al-Gayyar Mohammed M H , Eissa Laila A , Rabie Ahmed M , El-Gayar Amal M 
Published: February 2007

AbstractThere is an interactive relationship between leukaemia and oxidative stress. Leukaemic cells produce larger amounts of reactive oxygen species (ROS) than non-leukaemic cells as they are under a continual state of oxidative siege. So, this study was performed on 20 patients with chronic leukaemia from the Oncology Centre, Mansoura University. We measured leucocytic H2O2 concentrations and lipid peroxidation as serum malondialdehyde (MDA) concentration, serum total antioxidant activity, plasma ascorbic acid and dehydroascorbic acid concentrations, blood reduced glutathione concentration, haemolysate G6PD activity, blood catalase activity, serum superoxide dismutase (SOD) activity and serum anti-dsDNA concentration. We found that chronic leukaemia patients showed a significant increase (P &lt; 0.05) in leucocytic H2O2, serum MDA concentration and total anti-oxidant activity either before or after treatment as compared with control group. Also, there was a significant increase in the other parameters (glutathione, catalase and SOD) either before or after treatment, but we found a significant decrease in ascorbic acid concentration and G6PD activity. There was a significant increase in anti-dsDNA concentration either before or after treatment. It can be concluded that leukaemic patients produce larger amounts of ROS than non-leukaemic patients. Also, the increase in antioxidant activity in leukaemic patients is not high enough to counteract the harmful effects of free radicals. This scenario becomes worse after administration of chemotherapy.
Physico-chemical alterations of urine in experimental hyperoxaluria: a biochemical approach with fucoidan
Authors: Veena Coothan Kandaswamy , Josephine Anthony , Preetha Sreenivasan P , Varalakshmi Palaninathan 
Published: February 2007

Abstract
Urinary supersaturation-induced crystal formation has been attributed as one of the key factor for the pathogenesis/progression of lithogenesis. This study was aimed at investigating whether fucoidan, a naturally occurring sulfated glycosaminoglycan, could ameliorate the biochemical changes in urine induced by stone formation. Two groups of male albino Wistar rats (120 ± 20 g) received 0.75% ethylene glycol (EG) for 28 days to induce hyperoxaluria, and one of them received sulfated polysaccharides (fucoidan from Fucus vesiculosus, 5 mg kg−1, S.C.), commencing from the 8thday of the experimental period. One group was maintained as normal control group and another group served as drug control, which received sulfated polysaccharides. The urine collected from all the groups was analysed for changes in pH, volume, oxalate, calcium, phosphorus, uric acid, magnesium, citric acid and glycosaminoglycans. Urinary crystals were analysed with a light microscope. Renal tissues were studied under polarized light for deposition of crystals and also analysed for their oxalate and calcium content. The changes in extracellular matrix on crystal deposition were also evaluated. The urinary pH and volume were altered in rats treated with EG along with an increase in weight of the kidney. Further, administration of EG to rats increased the supersaturation of urine by escalating the levels of the stone-forming constituents, such as oxalate, calcium, phosphorus and uric acid, which was completely restored by fucoidan treatment. The decrease in the inhibitors, like citrate, magnesium and glycosaminoglycans, in urine was prevented by the co-treatment with fucoidan. In hyperoxaluric rats, there was an increased excretion of calcium oxalate monohydrate crystals in urine along with crystal deposition in renal tissues; this was prevented by fucoidan treatment. Fucoidan administration reversed even the tissue levels of calcium and oxalate. The increased accumulation of collagen and expression of transforming growth factor-β1 in hyperoxaluria was normalized on fucoidan administration. These results suggest that the physico-chemical alterations in urine produced during hyperoxaluria can be reversed by fucoidan administration.
β-Blocking activity of PP-34, a newly synthesized aryloxypropanolamine derivative, and its cardioprotective effect against ischaemia/reperfusion injury in laboratory animals
Authors: Bhatt Lokesh K , Nandakumar K , Bodhankar S L , Bansal Jyotika , Piplani Poonam 
Published: February 2007

Abstractβ-Adrenoceptor antagonists are widely used in cardiovascular medicine. However, the main side effect of these drugs is due to antagonism of β2-adrenoceptors in the airways, resulting in broncho-spasm. Therefore, more cardioselective β-blockers have been developed to offer a lower side effect profile. We have studied a new aryloxypropanolamine derivative (PP-34) with more cardioselectivity and efficacy against ischaemia/reperfusion injury in rats. Oxalate salts of 1-(tert-butylamino)-3-(5-tert-butylaminomethyl-2-methoxyphenoxy) propan-2-ol (PP-34) is a novel β-adrenoceptor antagonist. In-vitro studies in rat isolated right atria, guinea-pig trachea and rat distal colon preparations were carried out to investigate the potency of PP-34 towards different β-adrenoceptor subtypes. pA2/pKB values of PP-34 for β1, β2, and β3 adrenoceptor were 7.89 ± 0.15, 6.13 ± 0.09 and 6.30 ± 0.19, respectively. The β1/β2 selectivity ratio calculated was in the order of PP-34 &gt; atenolol &gt; propranolol. Pre-ischaemic administration (20 min before coronary occlusion) of PP-34 (0.3 or 1 mg kg−1) showed cardioprotective effects against ischaemia/reperfusion injury in rats and significantly reduced arrhythmias, infarct area and necrosis induced by ischaemia/reperfusion injury. The efficacy of PP-34 was found to be greater then atenolol. In conclusion, PP-34 is a cardioselective β-adrenoceptor antagonist, possessing potent anti-arrhythmic and cardioprotective effects against ischaemia/reperfusion injury in rats.
Improvement of hyperglycaemia and metabolic syndromes in type 2 diabetic KKAy mice by oral treatment with [meso-tetrakis(4-sulfonatophenyl) porphyrinato]oxovanadium(IV)(4-) complex
Authors: Saha Tapan Kumar , Yoshikawa Yutaka , Sakurai Hiromu 
Published: February 2007

Abstract
Recently, we reported that [meso-tetrakis(4-sulfonatophenyl)porphyrinato]oxovanadium(IV)(4-), VO(tpps), shows in-vitro insulin-mimetic and in-vivo anti-diabetic activity in streptozotocin (STZ)-induced type 1 diabetic mice. This result prompted us to examine its ability in type 2 diabetic model KKAy mice with insulin resistance. We studied the in-vivo anti-diabetic activity of VO(tpps), compared with that of vanadium(IV) oxide sulfate, VS, as control. Both compounds were orally administered at doses of 5–10 mg (0.1-0.2 mmol) V/kg body weight to the KKAy mice for 28 days. VO(tpps) normalized the hyperglycaemia within 15 days, while VS lowered the blood glucose concentration only by a small degree. In addition, metabolic syndromes characterized by insulin and leptin resistance were significantly improved in VO(tpps)-treated KKAy mice compared with those treated with VS. The improvement in diabetes was validated by oral glucose tolerance test and decrease in HbA1c concentration. Based on these observations, VO(tpps) is proposed to be an orally active oxovanadium(IV)-porphyrin complex for treating not only type 2 diabetes but also metabolic syndromes in animals.