bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of 5-Hydroxytryptamine on the Transintestinal Electrical Activity and Cardiovascular Function of Fawn-hooded Rats In-vivo
Authors: Hardcastle J , Hardcastle P T 
Published: July 2003

Abstract
Fawn-hooded rats, which have abnormal serotonergic function, were used to investigate the receptors involved in 5-hydroxytryptamine (5-HT)-induced intestinal secretion. The effects of 5-HT on secretion by the small intestine and proximal colon, monitored as increased transintestinal electrical activity, and on cardiovascular function, measured as changes in heart rate and blood pressure, were compared in fawn-hooded and Wistar rats.
The maximum fall in heart rate induced by 5-HT (mediated by 5-HT3 receptors) was greater in fawn-hooded than in Wistar rats. ED50 values (the doses resulting in 50% of the maximum effect) for the 5-HT2-mediated increases in systolic pressure were lower for both 5-HT and 5-methoxytryptamine in the fawn-hooded group. The prolonged fall in diastolic pressure mediated by 5-HT1-like receptors was significantly attenuated in fawn-hooded rats, with the maximum responses to 5-HT, 5-methoxytryptamine and 6-hydroxyindalpine reduced to 21%, 42% and 28%, respectively, of the values obtained for Wistar rats. In fawn-hooded rats the small intestine was less sensitive to the effects of 5-HT (ED50=47 nmol kg−1; ED50 for Wistar rats=23nmol kg−1) and the maximum colonic response to 5-methoxytryptamine wasgreater (7.0mV compared with 4.3 mV in Wistar rats), but other indices did not differ for the two strains. The responses to 6-hydroxy-indalpine were similar in fawn-hooded and Wistar rats.
It is concluded that although the cardiovascular response of fawn-hooded rats to 5-HT challenge is very different from that of Wistar rats, this difference is not reflected in marked alterations in 5-HT-induced intestinal secretion. This is consistent with 5-HT stimulating secretion via the activation of several different receptor subtypes so that any changes in the receptor profile in fawn-hooded rats results in little alteration in the overall intestinal response.
Effect of Pretreatment with FTY720 and Cyclosporin on Ischaemia-Reperfusion Injury of the Liver in Rats
Authors: Mizuta Koichi , Ohmori Masami , Miyashita Fujiko , Kitoh Yasuhiko , Fujimura Akio , Mori Masaya , Kanno Takayuki , Hashizume Kohei , Kobayashi Eiji 
Published: July 2003

Abstract
The effect of pretreatment with FTY720 (2-amino-2-[2-(4-octylphenyl)ethyl]-1,3-propane-diol hydrochloride) or cyclosporin, or both, on neutrophil-mediated injury has been examined by use of a rat model of transient clamping of hepatic flow.
Pretreatment with FTY720 alone or with cyclosporin induced a marked reduction of circulatory lymphocytes, whereas the use of these drugs in combination was very effective at suppressing the elevation of the number of peripheral polymorphonuclear neutrophils (PMN) after reperfusion. Pretreatment with cyclosporin, with or without FTY720, significantly reduced hepatic damage, whereas FTY720 alone tended to prolong hepatic damage. Pretreatment of cyclosporin alone, but not in combination with FTY720, significantly reduced the accumulation of PMN and led to lower myeloperoxidase levels in the damaged liver.
In conclusion, pretreatment with cyclosporin, with or without FTY720, reduced hepatic damage after warm ischaemia-reperfusion, whereas pretreatment with FTY720 alone tended to prolong this damage.
Modulation of Nitric Oxide-dependent Vascular and Platelet Function In-vitro by the Novel Phosphodiesterase Type-V Inhibitor, ONO-1505
Authors: Laight David W , Anggärd Erik E , Carrier Martin J 
Published: July 2003

Abstract
We have characterized the in-vitro modulation of both nitric oxide (NO)-dependent vasodilator activity and anti-platelet function by the novel type-V phosphodiesterase inhibitor, ONO-1505 (4-[2-(2-hydroxyethoxy)ethylamino]-2-(1H-imidazol-1-yl)-6-methoxyquinazoline methanesulphonate).
ONO-1505 elicited vasorelaxation in the rat isolated aorta. If the concentration of ONO-1505 was ≤10 μM the vasorelaxation was abolished by NG-nitro-L-arginine methyl ester (L-NAME), by methylene blue, and by endothelial denudation. Furthermore, pretreatment of the rat isolated aorta for 10 min with ONO-1505 in the presence of L-NAME potentiated vasorelaxation to the NO-donor, sodium nitroprusside. Similarly, ONO-1505, although having no effect on adenosine diphosphate (ADP)-induced rat platelet aggregation in-vitro, augmented established anti-aggregatory effects of sodium nitroprusside.
The data therefore show that the novel phosphodiesterase V inhibitor ONO-1505 augments endogenous and exogenous nitrovasodilator activity in-vitro; they also imply modulation of the NO pathway in the haemodynamic actions of this compound, previously reported in-vivo.
In-vivo and In-vitro Assessment of the Free-radical-scavenger Activity of Ginkgo Flavone Glycosides at High Concentration
Authors: Hibatallah Jalila , Carduner Charlotte , Poelman Marie-Christine 
Published: July 2003

Abstract
Free radicals are involved in numerous skin diseases, especially inflammatory reactions and photosenescence. To identify possible free-radical scavenging by an original terpenefree Ginkgo biloba extract containing 33% Ginkgo flavone glycosides, mostly quercetin and kaempferol derivatives, we studied its activity by means of in-vitro and in-vivo experiments, using superoxide dismutase (SOD) as a positive control.
By means of an in-vitro electron-spin resonance (ESR) assay we compared the activity of the Ginkgo extract with that of its two aglycones, quercetin and kaempferol. Quercetin and Ginkgo extract had significant antioxidant properties without pro-oxidant effect. In contrast, kaempferol, above an optimum antioxidant concentration, behaved as a pro-oxidant. The in-vivo experiments were conducted on an anti-inflammatory model. The cutaneous blood flux which reflects the skin inflammatory level was recorded by means of a laser Doppler perfusion imager. The data confirmed the free-radical-scavenging property of both Ginkgo extract and SOD. The Ginkgo extract significantly inhibited (37%) cutaneous blood flux to the same extent as SOD.
These data confirmed the antioxidant property of Ginkgo extract. A complementary spin-trapping technique would enable identification of the free radicals involved. This Ginkgo extract should be useful for protection of the skin against free radicals.
Isolation of Opioid-active Compounds from Tabernaemontana pachysiphon leaves
Authors: Ingkaninan K , Ijzerman A P , Taesotikul T , Verpoorte R 
Published: July 2003

Abstract
A procedure for prefractionation of crude plant extracts by centrifugal partition chromatography (CPC) has been developed to enable rapid identification of known-positive compounds or false-positive compounds and to increase the chance of identifying minor unknown-active compounds. The study explored the use of CPC as a tool in the prefractionation step before investigation of bioactivity.
Fractions obtained by CPC from an ethanolic extract of Tabernaemontana pachysiphon Stapf (Apocynaceae) were screened by means of an opiate-receptor-binding assay and an adenosine A1-receptor-binding assay. Fractions containing fatty acids, which had false-positive effects on the assay, were identified, as were unknown-positive fractions from which two opioid-active compounds, tubotaiwine and apparicine, were subsequently isolated. The affinities (Ki) of tubotaiwine and apparicine at the opiate receptor were 1.65 ± 0.81 and 2.65 ± 1.56 μmol, respectively. Both alkaloids had analgesic activity in the abdominal constriction test in mice.
CPC prefractionation led to the rapid isolation of two opioid-active compounds, tubotaiwine and apparicine, from the unknown-positive fraction; false-positive fractions were rapidly identified. Both tubotaiwine and apparicine had affinity for adenosine receptors in the micromolar range and also had in-vivo analgesic activity in mice.
Anti-inflammatory and Antinociceptive Effects in Rodents of the Essential Oil of Croton cajucara Benth
Authors: Bighetti Eliete J B , Hiruma-Lima Clélia A , Gracioso Juliano S , Brito Alba R M Souza 
Published: July 2003

Abstract
The plant Croton cajucara Benth. (Euphorbiaceae) is widely used in Amazonian folk medicine for the treatment of a wide range of illnesses. In this investigation the analgesic and anti-inflammatory properties of the essential oil from the bark of C. cajucara Benth., administered orally, were determined in several standard rodent models of pain and inflammation.
We observed that pretreatment with essential oil significantly reduced the latency of sleeping time evoked by pentobarbital compared with the control group (P &lt; 0.001). Doses of 100 or 1000 mg kg−1 also increased the sleeping time induced by pentobarbital (30.9 ± 3.91 and 52.1 ± 15.6 min, respectively) compared with the negative control (12.4 ± 4–27 min). We investigated the antinociceptive effect of the essential oil in chemical (acetic acid) and thermal (hot-plate) models of nociception in mice. Dipyrone (200 mg kg−1) and the highest doses of the essential oil (1000 mg kg−1) significantly inhibited acetic acid-induced abdominal constriction in mice (5.00 ± 1.38 and 6.8 ± 2.1 constrictions, respectively) compared with the negative control (33.1 ± 2). The same dose of essential oil also raised the pain thresholds of mice in the hot-plate test and significantly (P &lt; 0.05) increased the latency at all observation times. In acetic acid-induced abdominal constriction in mice pretreatment of the animals with naloxone (5 mg kg−1) significantly reversed the analgesic effect of morphine and of the essential oil at the highest dose (1000 mg kg−1).
The essential oil of C. cajucara was also investigated for its anti-inflammatory properties. At the lowest dose (100 mg kg−1) the essential oil had anti-inflammatory effects in animal models of acute (carrageenin-induced paw oedema in mice) and chronic (cotton pellet granuloma) inflammation. The essential oil at doses of 50, 100 and 200 mg kg−1 significantly and dose-dependently inhibited carrageenan-induced oedema (49 ± 5; 37 ± 5; 34 ± 8 mg, respectively) compared with the negative control (74 ± 8 mg). The essential oil (100 mg kg−1) also inhibited chronic inflammation by 38% whereas diclofenac inhibited it by 36%. However, the essential oil did not inhibit the migration of neutrophils into the peritoneal cavity.
These data show that the essential oil from C. cajucara contains compounds that had a significant antinociceptive effect when the oil was administered at the highest dose. This effect seems to be related to interaction with the opioid system. The essential oil also had a significant anti-inflammatory effect in acute and chronic inflammation models when administered at lower doses. This effect seems to be related to cyclooxygenase inhibition.
Investigation of Plants used in Jamaican Folk Medicine for Anti-bacterial Activity
Authors: Facey Petrea C , Pascoe Keith O , Porter Roy B , Jones Alcia D 
Published: July 2003

Abstract
We have started a systematic scientific study of folklore medicinal plants currently used as alternative medicine in Jamaican society. In this initial study, extracts of plants widely used by the islanders are studied for antibacterial activity against five common pathogens; Streptococcus group A, Staphylococcus aureus, Proteus mirabilis, Pseudomonas aeruginosa and Escherichia coli.
These studies revealed that 25% (approx.) of the plant extracts had antimicrobial activity against at least one of the microbes used. Subsequent to these observations, extracts from Mikania micrantha were examined in detail. This led to the isolation of two sesquiterpenoids, mikanolide and dihydromikanolide, with activity against S. aureus and C. albicans.
The results suggest that traditional folk medicine could be used as a guide in our continuing search for new natural products with potential medicinal properties.
Fluorimetric Determination of Ampicillin by use of Non-toxic Catalysts. Estimation of β-Lactamase Activity and Parameters
Authors: Baker W L 
Published: July 2003

Abstract
A fluorescence assay based on the use of biological reducing agents as catalysts rather than heavy metal ions has been developed for estimation of ampicillin concentrations.
The assay is based on the conversion of ampicillin to its penicilloate, by treatment with sodium hydroxide, then neutralization, dilution with 0.5 M acetate buffer at pH4 and heating for 30 min at 100°C in the presence of ascorbic acid (0.5 mg) and EDTA (50 μM). Reduced glutathione, cysteine and N-acetylcysteine also catalysed the development of fluorescence. A practical sensitivity range of 0.5–50 μM ampicillin was used. The assay was used to estimate ampicillin in some biological solutions to which the antibiotic has been added. Milk, blood serum, trypticase soy broth and nutrient broth containing 25 μM antibiotic assayed at 18.5, 21.7, 16.5 and 14.7 μM, respectively, with standard deviations between 1.2 and 0.7%. The low results were attributed to binding of some ampicillin by proteins or peptides which were removed by pretreatment. Urine containing 5 mM ampicillin assayed at 4.97 mM with a standard deviation of 3%. A modification of the procedure was used to measure β-lactamase activity against ampicillin in several organisms in a fixed time assay. Kinetic parameters of a commercial β-lactamase preparation from Bacillus cereus could also be determined by an additional modification. In both instances a correction was required for the intrinsic fluorescence of ampicillin remaining in the solution. The preparation examined had a Michaelis constant (Km) of 0.32 mM, a maximum velocity (Vcat) of 5398 μmol ampicillin hydrolysed mg−1 min−1, an apparent catalytic constant (Kcat, turnover number) of 20220 s−1 and a Kcat/Km ratio of 0.63 times 107 M−1 S−1.
The major advantage of using this assay technique is that toxic metals are not used in the development of fluorescence so it is more environmentally acceptable. The technique is useful for examining β-lactamase activity against ampicillin and might be useful for pharmaceutical products—for determining available therapeutic levels and for monitoring the activity of penicillin acylase against the penicilloate of ampicillin.
Evaluation and Prediction of Drug Permeation
Authors: Pagliara Alessandra , Reist Marianne , Geinoz Sandrine , Carrupt Pierre-Alain , Testa Bernard 
Published: July 2003

Abstract
A major challenge confronting the pharmaceutical scientist is to optimize the selective and efficient delivery of new active entities and drug candidates. Successful drug development requires not only optimization of specific and potent pharmacodynamic activity, but also efficient delivery to the target site. Following advances in rational drug design, combinatorial chemistry and high-throughput screening techniques, the number of newly discovered and promising active compounds has increased dramatically in recent years, often making delivery problems the rate-limiting step in drug research. To overcome these problems, a good knowledge of the pharmacokinetic barriers encountered by bioactive compounds is required. This review gives an overview of the properties of relevant physiological barriers and presents some important biological models for evaluation of drug permeation and transport. Physicochemical determinants in drug permeation and the relevance of quantitative and qualitative approaches to the prediction and evaluation of passive drug absorption are also discussed.
Biochemical and Pharmacological Characteristics of a Newly Synthesized H+/K+-ATPase Inhibitor, YJA20379-8, 3-Butyryl-4-[R-1-methylbenzylamino]-8-ethoxy-1,7-naphthyridine, in pigs and rats
Authors: Sohn Sang Kwon , Chang Man Sik , Choi Wahn Soo , Chung Young Kuk , Kim Kyu Bong , Woo Tae Wook , Lee Seok Bong , Park Chong Jeun 
Published: July 2003

Abstract
We have investigated the effect of the newly synthesized proton-pump inhibitor YJA20379-8, 3-butyryl-4-[R-1-methylbenzylamino]-8-ethoxy-1,7-naphthyridine, on gastric mucosal proton pump (H+/K+-ATPase) activity, gastric acid secretion and gastric lesions in experimental animals.
In lyophilized pig gastric microsomes, YJA20379-8 was shown to inhibit H+/K+-ATPase activity; the inhibitory effect was not affected by pH, the IC50 (dose resulting in 50% inhibition) being 28.0 μM and 30.0 μM at pH 6.4 and pH 7.4, respectively. The effect was fully reversed by dilution and subsequent washing of the incubation mixtures of H+/K+-ATPase and YJA20379-8, suggesting the reversible nature of the enzyme inhibition. In pylorus-ligated rats, YJA20379-8 administered by different routes (intraduodenal, subcutaneous, intravenous or oral) resulted in dose-dependent suppression of basal gastric acid secretion. The duration of antisecretory action of 30 mg kg−1 YJA20379-8 given intraduodenally was very brief (less than 7 h). Pretreatment with YJA20379-8 also dose-dependently prevented gastric lesions induced by absolute ethanol and water-immersion stress in rats.
These results suggest that YJA20379-8 might exert its antiulcer activity partly by reversible suppression of acid secretion and partly by protecting the gastric mucosa against ulcerative stimuli.
Inclusion Complexation of the Sunscreen Agent 2-Ethylhexyl-p-dimethylaminobenzoate with Hydroxypropyl-β-cyclodextrin: Effect on Photostability
Authors: Scalia Santo , Villani Silvia , Casolari Alberto 
Published: July 2003

Abstract
The interaction between the UV filter, 2-ethylhexyl-p-dimethylaminobenzoate, and unmodified and modified α-, β- or γ-cyclodextrins was studied in water by phase-solubility analysis.
Of the cyclodextrins available, only hydroxypropyl-β-cyclodextrin caused a marked increase in the aqueous solubility of 2-ethylhexyl-p-dimethylaminobenzoate. The data from the solubility study indicated the formation of a 1:1 (sunscreen-cyclodextrin) complex. The inclusion of the sunscreen agent into the hydroxypropyl-β-cyclodextrin cavity was confirmed by thermal analysis and by nuclear magnetic resonance spectroscopy. Irradiation-induced degradation of 2-ethylhexyl-p-dimethylaminobenzoate was reduced by complexation with hydroxypropyl-β-cyclodextrin, this effect being more pronounced in solution (the extent of degradation was 25.5% for the complex compared with 54.6% for free 2-ethylhexyl-p-dimethylaminobenzoate) than in the emulsion vehicle (the extent of degradation was 25.1% for the complex compared with 33.4% for free 2-ethylhexyl-p-dimethylaminobenzoate).
Although photodegradation of the sunscreen agent is significantly reduced by formation of the inclusion complex it is important to design a suitable vehicle. Inclusion of 2-ethyl-hexyl-p-dimethylaminobenzoate-DMAB into the hydroxypropyl-β-cyclodextrin cavity limits interaction of the UV filter with the skin reducing the side-effects of the formulation.
Absorption of Vitamin K2 by Dogs after Oral Administration of a Soft Gelatin Capsule Formulation Containing a New Emulsion-type Vehicle
Authors: Amemiya Tohru , Mizuno Satoshi , Hayashi Yayoi , Yuasa Hiroaki , Watanabe Jun 
Published: July 2003

Abstract
This study has evaluated the performance of a newly developed vehicle for administration of a drug in a soft gelatin capsule. The absorption of vitamin K2 in dogs after oral administration of the vitamin in a soft gelatin capsule containing the newly developed vehicle was compared with absorption after administration of a control formulation prepared by encapsulating the contents of a commercially available vitamin K2 capsule (Glakay capsules 15 mg) in the same type of soft gelatin.
Under non-fasted conditions the profile of the plasma concentration of vitamin K2 against time for the test formulation was comparable with that for the control formulation in non-fasted dogs. Under fasted conditions, however, both the maximum concentration (Cmax) and the area under the plot of concentration against time (AUC) were significantly smaller for the test formulation than for the control formulation. The Cmax and AUC for the test formulation were about 10 times larger for non-fasted dogs than for fasted dogs whereas values for the control formulation were about twice as large. These results suggest that both formulations might require the presence of food or digestive fluid components, or both, for better absorption of vitamin K2. It seems that although the performances of the test and control formulations were comparable in the presence of these components, the control formulation works better in their absence. It should be also noted that, in contrast with the results from the absorption tests, the dispersibility of the test vehicle in water was much better than that of the control vehicle. This suggests that dispersibility does not significantly affect vitamin K2 absorption.
In conclusion, although the new vehicle did not perform better than the control vehicle in terms of vitamin K2 absorption, the performance of the control formulation was comparable for non-fasted dogs. Because the new vehicle contains considerably less surfactant than the vehicles currently used in soft gelatin capsules, it could be a safer alternative for use under non-fasted conditions.
Statistical Moments for Placental Transfer of Solutes in Man
Authors: Bernus Iren , Roberts Michael S , Rasiah Rohan L , Mortimer Robin H 
Published: July 2003

Abstract
The placental transfer of red blood cells and solutes in man has been investigated by statistical moment analysis, using the impulse-response technique. Model compounds of different lipophilicity (sucrose, water, antipyrine, propranolol and labetalol) were injected with a vascular reference (labelled red blood cells) as boluses into either the foetal or maternal circulation of a single-pass perfused placental lobule. Maternal and foetal venous outflow fractions were collected at intervals ranging from 1 to 600s. Perfusion was conducted at maternal flow rates of 4 and 6 mL min−1 and foetal flow rates of 2 and 3 mL min−1, respectively, to yield a constant materno-foetal flow ratio of 2. The outflow concentration-time profile curves were analysed by statistical moment analysis.
The sum of foetal and maternal recovery was close to 100% for red blood cells, sucrose, water and antipyrine, but lower for propranolol and labetalol. The mean transit time (MTT) values ranged from 20 to 500s. The normalized variance (CV2) for red blood cells in the foetal and maternal circulation of the placenta were in the ranges 2.31 to 3.86 and 2.00 to 2.03, respectively.
The shape of the outflow concentration-time proifles after bolus input is consistent with that of vascular residence time models such as the dispersion model. The heterogeneity in red blood cell transit times, as defined by CV2, is greater than in either the perfused leg or perfused liver.