bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of oxotremorine-induced desensitization of guinea-pig ileal longitudinal muscle in Ca2+-free conditions
Authors: Horio Shuhei , Fukui Hiroyuki 
Published: July 2003

Abstract
The aim of this study was to investigate the differences between oxotremorine-induced and acetylcholine (ACh)-induced desensitization, particularly under Ca2+-free conditions, in guinea-pig ileal longitudinal muscle, and to elucidate the different mechanisms of desensitization that might exist between these two muscarinic agonists. Pretreatment of the tissue with 10−7 — 10−5 M oxotremorine (desensitizing treatment) in normal Tyrode solution caused desensitization of the responses to ACh, as did the desensitizing treatment with ACh. However, Ca2+-free conditions significantly reduced oxotremorine-induced desensitization, contrary to the previous findings that Ca2+-free conditions enhanced ACh-induced desensitization. The desensitizing treatment with oxotremorine caused suppression of the responses to high K+ (tonic phase), as did the ACh treatment. Ca2+-free conditions removed this suppression, whereas this condition enhanced ACh-induced suppression of the K+ response. A protein kinase C inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (10−4 M) had no effect on oxotremorine-induced desensitization of the ACh response. The results suggest that a voltage-gated Ca2+ channel was involved in oxotremorine-induced desensitization, as in ACh-induced desensitization, but that the process of inactivation of Ca2+ channels was different between oxotremorine and ACh, and that oxotremorine-induced desensitization was due not only to Ca2+ channel, but also to other unknown factors. Protein kinase C did not participate in oxotremorine-induced desensitization.
Preparation and characterization of biodegradable or enteric-coated microspheres containing the protease inhibitor camostat
Authors: Uchida Takahiro , Yasuda Noriko , Matsuyama Kenji 
Published: July 2003

Abstract
We have produced biodegradable or enteric-coated microspheres containing camostat mesylate, a protease inhibitor, using a water-oil-water emulsion solvent evaporation method. The characteristics of the microspheres were determined. When polylactic acid, a biodegradable polymer, was used as a wall material, the optimized microsphere obtained showed a loading efficiency of almost 95% and had a mean diameter of 30 pim. This microsphere showed a sustained-release profile, with nearly 25% of drug being released at seven days in a dissolution test. When hypromellose acetate succinate (AS-HG type, with a high content of succinyl group) was used as an enteric wall material, optimized microspheres showed a loading efficiency of almost 80%. In this case, pH 3.0 citrate buffer was used as an internal aqueous phase, and citrate buffer containing 0.5 % polyvinylalcohol was used as the external aqueous phase. These microspheres showed a rapid release profile in pH 6.8 buffer, whereas the release was extremely slow in pH 1.2 buffer. Hypromellose acetate succinate microspheres were also prepared containing 10% (w/w) N-benzoyl-dl-arg-4-nitroanilide as a model substrate for trypsin, with or without 5% (w/w) camostat. These microspheres were incubated in pH 6 or 7 buffer containing trypsin at 37°C. When camostat was included in the microspheres, the substrate was protected from attack by trypsin, while in the absence of camostat, the released substrate was immediately attacked by trypsin to produce the degradation product N-benzoyl-dl-arginine.
A sensitive and reliable method for the detection of lipid peroxidation in biological tissues
Authors: Anoopkumar-Dukie Shailendra , Walker Roderick B , Daya Santy 
Published: July 2003

Abstract
A simple, accurate and cost effective method has been designed for the determination of lipid peroxidation in biological tissue samples. The method was a modification and improvement on existing methods available for lipid peroxidation determination. Solid-phase extraction was used to separate the thiobarbituric acid-malondialdehyde complex from thiobarbituric acid-reactive substances and HPLC was performed using a C18 (Waters Spherisorb, 5μm, 250 × 4.6 mm i.d.) column to achieve isolation of the complex. The procedure was validated with respect to linearity of calibration (0.998), precision, sensitivity and limits of quantitation (1 nmol mL−1) and detection (0.5 nmol mL-1). Resorcinol was used as an external standard. The method was tested by inducing free radical generation with a known free radical generator, quinolinic acid, in rat brain homogenate. The results showed that the method presented allowed detection of lipid peroxidation products at concentrations in the nanomolar (nM) range compared with the micromolar (μM) range detected by other methods, thus rendering it suitable for use with biological samples. In addition, the modified method allowed for detection of the purified lipid peroxidation products, thus eliminating the possibility of simultaneous detection of impurities that absorb at the same wavelength.
Synthesis and in-vitro antimicrobial activity of new 1,2,4-triazoles
Authors: Bhat A R , Bhat G Varadaraj , Shenoy G Gautham 
Published: July 2003

Abstract
We have described the synthesis of new 1,2,4-triazoles and have evaluated their antimicrobial profile. Antitubercular activity was determined in triplicate using the Lowenstein-Jensen medium. A loopful of Mycobacterium tuberculosis suspension was inoculated on the surface of each Lowenstein-Jensen media containing the test compounds (100, 10 or 1 μg mL−1). To evaluate in-vitro antibacterial activity, compounds (50, 5 or 0.5 μg) were evaluated against B. subtilis, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Staphylococcus typhi by the disc diffusion method. To evaluate antifungal activity Sabourauds Dextrose agar medium was used. Some of the compounds (5, 0.5 or 0.05 μg mL−1) were screened for activity against Aspergillus niger 88 and Aspergillus niger 90 and others were screened for activity against T. rubrum TR1, T. rubrum R6, T. rubrum R7 and T. mentagrophyte M1, using the cup plate method. Our results show that the triazoles with a pyrazine moiety at position 3 were more active as antitubercular and antifungal agents compared with the triazoles which had a pyrazine moiety at position 4 of the molecule.
Stimulation of insulin release in rats by Die-Huang-Wan, a herbal mixture used in Chinese traditional medicine
Authors: Cheng Juei-Tang , Liu I-Min , Chi Tzong-Cherng , Su Hui-Chen , Chang Chung-Gwo 
Published: July 2003

Abstract
Die-Huang-Wan is a herbal mixture widely used in Chinese traditional medicine to treat diabetic disorders. We have investigated the effect of Die-Huang-Wan on plasma glucose concentration in-vivo. Die-Huang-Wan was administered orally (5.0, 15.0 or 26.0 mg kg−1) to three rat models. Wistar rats were used as the normal animal model, rats with insulin-resistance (induced by the repeated thrice daily injection of human long-acting insulin) were used as the non-insulin-dependent diabetic model, and streptozotocin-induced diabetic rats were used as the insulin-dependent diabetic model. In normal rats, approximately 1 h after oral administration of Die-Huang-Wan the plasma glucose concentration decreased significantly in a dose-dependent manner, from 5 to 26.0 mg kg−1. A similar effect was observed in rats with insulin-resistance. However, this effect was not observed in streptozotocin-induced diabetic rats, even at an oral dose of 26.0 mg kg−1. These results suggested an insulin-dependent action, a view supported by the increase of plasma insulin-like immunoreactivity in normal rats receiving Die-Huang-Wan. The results indicated that Die-Huang-Wan had an ability to stimulate the secretion of insulin and this preparation seemed helpful in improving the diabetic condition, especially hyperglycaemia in type-II diabetes.
Role of nitric oxide in hypodipsia of rats with obstructive cholestasis
Authors: Mani Ali Reza , Nahavandi Arezo , Mani Amir Hossein , Dehpour Ahmad Reza 
Published: July 2003

Abstract
Cholestasis is associated with the overproduction of nitric oxide (NO), and NO acts as an inhibitory mechanism when thirst is stimulated by water deprivation or by angiotensin II. Due to the presence of hypodipsia in the cholestatic condition, we have compared the rate of water intake between bile duct-ligated (cholestatic) and sham-operated rats. We have evaluated the effect of NO synthesis inhibition by NG-nitro-L-arginine (L-NNA, 10 mg kg−1/day) on the rate of water intake in cholestatic rats. The results showed that plasma alkaline phosphatase activity (a marker of liver damage) increased after bile-duct ligation, and that its elevation was partially (but significantly) prevented by treatment with L-arginine. A two-week bile-duct obstruction induced a significant decrease in the rate of water intake compared with sham-operated animals (35.87 ± 1.45 vs 42.37 ± 1.99 mL/day, P &lt; 0.05). This effect was corrected by the daily administration of L-NNA. Surprisingly, L-arginine (200 mg kg−1/day) showed similar activity as L-NNA in cholestatic rats and increased water intake, but not in control animals. Systemic NO synthesis inhibition corrected the decrease in water intake observed in cholestatic rats. This suggests an important role for NO in the pathophysiology of hypodipsia in cholestatic subjects. The effect of chronic L-arginine administration observed in cholestatic rats but not seen in the control rats could be explained theoretically by the amelioration of cholestasis-induced liver damage by chronic L-arginine administration in bile duct-ligated rats.
Pharmacognosy in the 21st century
Authors: Kinghorn A Douglas 
Published: July 2003

AbstractThe term pharmacognosy as a constituent scientific discipline of pharmacy has been in use for nearly 200 years, and it refers to studies on natural product drugs. During the last half of the 20th century, pharmacognosy evolved from being a descriptive botanical subject to one having a more chemical and biological focus. At the beginning of the 21st century, pharmacognosy teaching in academic pharmacy institutions has been given new relevance, as a result of the explosive growth in the use of herbal remedies (phytomedicines) in modern pharmacy practice, particularly in western Europe and North America. In turn, pharmacognosy research areas are continuing to expand, and now include aspects of cell and molecular biology in relation to natural products, ethnobotany and phytotherapy, in additiontothe more traditional analytical method development and phytochemistry. Examples are provided in this review of promising bioactive compounds obtained in two multidisciplinary natural product drug discovery projects, aimed at the elucidation of new plant-derived cancer chemotherapeutic agents and novel cancer chemopreventives, respectively. The systematic study of herbal remedies offers pharmacognosy groups an attractive new area of research, ranging from investigating the biologically active principles of phytomedicines and their mode of action and potential drug interactions, to quality control, and involvement in clinical trials.
Increased vigabatrin entry into the brain by polysorbate 80 and sodium caprate
Authors: Dimitrijevic D , Whitton P S , Domin M , Welham K , Florence A T 
Published: July 2003

Abstract
The effects of a non-ionic surfactant, polysorbate 80, and the sodium salt of the saturated fatty acid, sodium caprate (C10), as potential brain absorption enhancers for vigabatrin were studied. Vigabatrin is an enzyme-activated irreversible inhibitor of γ-aminobutyric acid (GABA) transaminase that increases brain and cerebrospinal GABA concentrations in animals and man. Before intravenous administration, a range of concentrations of the surfactants were tested using erythrocyte lysis or the red blood cell lysis test to establish the non-toxic concentration range. Vigabatrin was dissolved in 0.1% polysorbate 80 and 0.1% sodium caprate and administered intravenously in doses of 4 mL kg−1 to male Wistar rats (230–250 g; n = 3). Rats were killed 2 h after drug and surfactant administration and the brains were immediately removed and homogenized in 0.4m perchloric acid. Selected ion monitoring electrospray mass spectrometry was used to determine the concentration of vigabatrin and GABA directly from the perchloric acid extract of the rat brain. This method was developed to increase the speed and efficiency of the analysis by removing the need for complex extraction and derivatization procedures while retaining the specificity of the mass spectrometer as a detector. The stability of both vigabatrin and GABA in perchloric acid was established by monitoring their pseudo molecular ions in standard solutions at timed intervals over 24 h. Although the detection level for vigabatrin and GABA was at least 50 pg, only GABA was detected in rat brain. Vigabatrin caused a small increase in whole brain GABA. However, GABA levels were higher in the samples with vigabatrin + enhancer than in the samples where vigabatrin alone was administered. One-way analysis of variance indicated a significant effect of the surfactants on GABA levels (F (5,17) = 11.86, P &lt; 0.01) and vigabatrin absorption was presumed. The rectal temperature of the rats is lowered by the presence of vigabatrin in the brain. Vigabatrin alone decreased rectal temperature by 6%. When given with either polysorbate 80 or sodium caprate, the extent of temperature lowering was significantly greater (P &lt; 0.001). There was no significant difference after 2 h between polysorbate 80 + vigabatrin, and sodium caprate + vigabatrin.
In-vitro and in-vivo evaluation of pH-responsive polymeric micelles in a photodynamic cancer therapy model
Authors: Taillefer J , Brasseur N , van Lier J E , Lenaerts V , Garrec D Le , Leroux J-C 
Published: July 2003

Abstract
pH-sensitive polymeric micelles of randomly and terminally alkylated N-isopropylacrylamide copolymers were prepared and characterized. Aluminium chloride phthalocyanine (AlClPc), a second generation sensitizer for the photodynamic therapy of cancer, was incorporated in the micelles by dialysis. Their photodynamic activities were evaluated in-vitro against EMT-6 mouse mammary tumour cells and in-vivo against EMT-6 tumours implanted intradermally on each hind thigh of Balb/c mice. pH-sensitive polymeric micelles were found to exhibit greater cytotoxicity in-vitro than control Cremophor EL formulations. In the presence of chloroquine, a weak base that raises the internal pH of acidic organelles, in-vitro experiments demonstrated the importance of endosomal/lysosomal acidity for the pH-sensitive polymeric micelles to be fully effective. Biodistribution was assessed by fluorescence of tissue extracts after intravenous injection of 2 μmol kg−1 AlClPc. The results revealed accumulation of AlClPc polymeric micelles in the liver, spleen and lungs, with a lower tumour uptake than AlClPc Cremophor EL formulations. However, polymeric micelles exhibited similar activity in-vivo to the control Cremophor EL formulations, demonstrating the higher potency of AlClPc polymeric micelles when localized in tumour tissue. It was concluded that polymeric micelles represent a good alternative to Cremophor EL preparations for the vectorization of hydrophobic drugs.
Encapsulation of bovine serum albumin in poly(lactide-co-glycolide) microspheres by the solid-in-oil-in-water technique
Authors: Castellanos Ingrid J , Carrasquillo Karen G , López Jesiebel De Jésus , Alvarez Mariali , Griebenow Kai 
Published: July 2003

Abstract
Non-aqueous protocols to encapsulate pharmaceutical proteins into biocompatible polymers have gained much attention because they allow for the minimization of procedure-induced protein structural perturbations. The aim of this study was to determine if these advantages could be extended to a semi-aqueous encapsulation procedure, namely the solid-in-oil-in-water (s/o/w) technique. The model protein bovine serum albumin (BSA) was encapsulated into poly(lactide-co-glycolide) (PLG) microspheres by first suspending lyophilized BSA in methylene chloride containing PLG, followed by emulsification in a 1% aqueous solution of polyvinyl alcohol). By variation of critical encapsulation parameters (homogenization intensity, BSA:PLG ratio, emulsifier concentration, ratio of organic to aqueous phase) an encapsulation efficiency of &gt; 90 % was achieved. The microspheres obtained showed an initial burst release of &lt; 20 %, a sustained release over a period of about 19 days, and a cumulative release of at least 90% of the encapsulated BSA. Different release profiles were observed when using different encapsulation protocols. These differences were related to differences in the microsphere erosion observed using scanning electron microscopy. Release of BSA was mainly due to simple diffusion orto both diffusion and microsphere erosion. Fourier-transform infrared studies were conducted to investigate the secondary structure of BSA during the encapsulation. Quantification of the α-helix and β-sheet content as well as of overall structural changes showed that the secondary structure of encapsulated BSA was not more perturbed than in the lyophilized powder used initially. Thus, the encapsulation procedure did not cause detrimental structural perturbations in BSA. In summary, the results demonstrate that the s/o/w technique is an excellent alternative to the water-in-oil-in-water technique, which is still mainly used in the encapsulation of proteins in PLG microspheres.
Pharmacokinetics of diaspirin cross-linked haemoglobin in a rat model of hepatic cirrhosis
Authors: Palaparthy R , Kastrissios H , Gulati A 
Published: July 2003

Abstract
The aim of the study was to evaluate the effect of cirrhosis on the disposition of the haemoglobin-based oxygen carrier, diaspirin cross-linked haemoglobin (DCLHb). Cirrhosis was induced in male Sprague-Dawley rats (200–250 g) by inhalational exposure to carbon tetrachloride (CCl4), over a period of 6 weeks. Pharmacokinetic evaluation was performed after a single intravenous bolus administration of DCLHb (400 mg kg−1). Serum biochemistry, including aspartate transaminase, alkaline phosphatase, bile acids, serum albumin, and serum creatinine, were measured in CCl4-treated (n = 6) and age-matched control (n = 6) rats. After 6 weeks, the jugular vein and carotid artery were cannulated for bolus DCLHb administration (400 mg kg−1) and blood sampling, respectively, in both groups of rats. Cirrhosis produced significant (P &lt; 0.05) elevations in alkaline phosphatase (497.4 ± 84.8 U L−1 vs 241.2 ± 5.1 U L−1), aspartate transaminase (920.5 ± 190.9 U L−1 vs 238.2 ± 118.1 U L−1) and bile acids (333.8 ± 77.3 mg dL−1 vs 43.8 ± 4.2 mg dL−1) compared with the control group. No significant renal dysfunction was observed as a result of CCl4 exposure. Plasma DCLHb concentrations declined approximately log-linearly. Systemic clearance of DCLHb was estimated to be 2.2 ± 0.7 mL h−1 in the treatment group and was slightly, but not significantly, less in the control group (3.6 ± 1.7 mL h−1). There was also a trend toward a longer elimination half-life in the treatment group (4.7 ± 2.2 h) compared with the control group (3.8 ± 0.8 h), although this difference was not statistically significant. Cirrhosis does not significantly alter the disposition of DCLHb perhaps due to increased extra-hepatic metabolism by the reticulo-endothelial system.
Antimicrobial activity of tannin components from Vaccinium vitis-idaea L.
Authors: Ho K Y , Tsai C C , Huang J S , Chen C P , Lin T C , Lin C C 
Published: July 2003

Abstract
Reactive oxygen species have been implicated as important pathological mediators in many clinical disorders, including periodontal disease. As a possible alternative for the treatment of periodontal disease, the antimicrobial activity of six tannins isolated from Vaccinium vitis-idaea L., with confirmed antioxidant activity, were assayed by the agar dilution method against selected periodontal pathogens, Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis and Prevotella intermedia. The results showed that epicatechin-(4β → 8)-epicatechin-(4β → 8, 2β → O → 7)-catechin had strong antimicrobial activity against P. gingivalis and P. intermedia, but not A. actinomycetemcomitans. The other tannins tested did not show antimicrobial activity. We conclude that tannins isolated from V. vitis-idaea L. with antimicrobial activity could potentially be used for the treatment of periodontal disease.
Evaluation of anti-inflammatory potential of Bergenia ciliata Sternb. rhizome extract in rats
Authors: Sinha Sanghamitra , Murugesan T , Maiti Kuntal , Gayen Jiaur Rahaman , Pal M , Saha B P 
Published: July 2003

Abstract
The methanol extract of the rhizome of Bergenia ciliata Sternb. (Saxifragaceae) has been evaluated for anti-inflammatory potential using two acute rat models (carrageenan- and serotonin (5-HT)-induced rat paw oedema) and a chronic rat model (cotton pouch-induced granuloma). Phenylbutazone (100 mg kg−1), a non-steroidal anti-inflammatory agent, was used as a standard. The methanol extract (100, 200 or 300 mg kg−1) exhibited significant (P &lt; 0.05) anti-inflammatory activity in all the animal models. At 300 mg kg−1 the methanol extract exhibited maximum inhibition of 32.4 ± 2.89% in carrageenan-induced rat paw oedema while the standard showed an inhibition of 44.1 ± 2.7% after 3 h of drug treatment. In the serotonin-induced rat paw oedema model, 300 mg kg−1 methanol extract suppressed oedema by 45.33 ± 2.09%, whereas the standard produced an inhibition of 53.5 ± 4.3%. In the cotton pouch granuloma model the methanol extract inhibited significantly (P &lt; 0.001) the granuloma weight in a dose-dependent manner. In this model, 300 mg kg−1 extract produced a maximum inhibition of 31.4 ± 1.09% in granuloma weight compared with 41.1 ± 1.32% reduction in granuloma weight for the standard. The methanol extract of B. ciliata exhibited significant anti-inflammatory potential at the dose levels examined.
Anti-fibrotic effects of a hot-water extract from Salvia miltiorrhiza roots on liver fibrosis induced by biliary obstruction in rats
Authors: Nan Ji-Xing , Park Eun-Jeon , Kang Hee-Chul , Park Pil-Hoon , Kim Ji-Young , Sohn Dong Hwan 
Published: July 2003

Abstract
The anti-fibrotic effects of a hot-water extract form the traditional Chinese medicinal herb Salvia miltiorrhiza (Labiatae) on liver fibrosis induced by biliary obstruction was studied in rats. Liver fibrosis was induced in male Sprague-Dawley rats by bile duct ligation and scission (BDL). After surgery, the hot-water extract of S. miltiorrhiza roots (100 mg kg−1, p.o.) was administered daily for 28 days. The concentrations of aspartate transaminase, alanine transaminase, alkaline phosphatase, total bilirubin and total cholesterol in serum and hydroxyproline and malondialdehyde contents in liver were significantly increased in BDL rats. Treatment with the extract of S. miltiorrhiza significantly reduced (P &lt; 0.01) the serum aspartate transaminase, alanine transaminase, alkaline phosphatase, and total cholesterol concentrations in BDL rats. The liver hydroxyproline content in BDL rats treated with extract was also reduced to 68% of that in BDL control rats (P &lt; 0.01). The liver malondialdehyde content in BDL rats treated with the extract was also reduced to 47% of that in BDL control rats (P &lt; 0.01). The morphological characteristics of fibrotic livers were improved in BDL rats treated with extract. Immunohistochemical examination of fibrotic liver showed that the extract of S. miltiorrhiza markedly reduced protein expression of α-smooth muscle cell-like actin, which indicates that hepatic stellate cell activation was inhibited during liver fibrosis development. The results indicate that the hot-water extract of S. miltiorrhiza roots inhibits fibrosis and lipid peroxidation in rats with liver fibrosis induced by biliary obstruction.