bluuebunny/crossref_metadata_2025_split huggingface dataset:
N-Methyl-d-aspartate Receptor Antagonists Enhance the Head-twitch Response, a 5-Hydroxytryptamine2 Receptor-mediated Behaviour, in Reserpine-treated Mice
Authors: Kim Hack-Seang , Park In-Sook , Lim Hwa-Kyung , Choi Hong-Serck , Oh Seikwan , Park Woo-Kyu , Jang Choon-Gon , Kim Seung-Hwan , Chang Myung-Jei 
Published: October 2002

Abstract
In this study, N-methyl-d-aspartate (NMDA)-receptor antagonists enhanced the head-twitch response induced by 5-hydroxytryptamine (5-HT) in reserpine-treated mice.
To minimize the risk of any indirect involvement of NMDA-receptor antagonists (d(-)-2-amino-5-phosphonopentanoic acid (AP-5), l(-)-3-(2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid (CPP), (+)-5-methyl-10,11-dihydroxy-5H-dibenzo-[a,d]-cyclohepten-5,10-imine (MK-801), ketamine, dextrorphan and dextromethorphan) with 5-HT neurones, vesicle stores of monoamines, especially 5-HT, were depleted with reserpine. In addition, the enhancement of 5-HT-induced head-twitch response was inhibited by apomorphine and NMDA as well as ritanserin in reserpine-treated mice.
These results support our previous conclusion that NMDA receptors play important roles in the glutamatergic modulation of 5-HTergic function at the postsynaptic 5-HT2 receptors in mice.
Gelatin Microspheres as a Pulmonary Delivery System: Evaluation of Salmon Calcitonin Absorption
Authors: Morimoto Kazuhiro , Katsumata Hideyuki , Yabuta Toshiyuki , Iwanaga Kazunori , Kakemi Masawo , Tabata Yasuhiko , Ikada Yoshito 
Published: October 2002

Abstract
The use of negatively and positively charged gelatin microspheres for pulmonary delivery of salmon calcitonin was examined in rats. The microspheres were prepared using acidic gelatin (isoelectric point (IEP):, 5.0) and basic gelatin (IEP, 9.0) for the negatively and positively charged microspheres, respectively. The average diameters of positively charged gelatin microspheres in the dry state were 3.4, 11.2, 22.5 and 71.5 μm, and that of negatively charged gelatin microspheres was 10.9 μm. Neither positively nor negatively charged gelatin microspheres underwent any degradation in pH 7.0 PBS and there was less than 8% degradation in bronchoalveolar lavage fluid (BALF) after 8 h. In in-vitro release studies in pH 7.0 PBS, salmon calcitonin was rapidly released from positively charged gelatin microspheres within 2 h, and its cumulative release was approximately 85%. In addition, the release profiles were not influenced by particle sizes. The release rates of salmon calcitonin from negatively charged gelatin microspheres were lower than that from positively charged gelatin microspheres. The cumulative release was approximately 40% after 2 h, but there was no evidence of any sustained release.
The pulmonary absorption of salmon calcitonin from gelatin microspheres was estimated by measuring its hypocalcaemic effect in rats. The pharmacological availability after administration of salmon calcitonin in positively and negatively charged gelatin microspheres was significantly higher than that in pH 7.0 PBS. The pharmacological availability after administration of salmon calcitonin in positively charged gelatin microspheres was significantly higher than that in negatively charged gelatin microspheres. Administration of salmon calcitonin in positively charged gelatin microspheres with smaller particle sizes led to a higher pharmacological availability. The pharmacological availability after pulmonary administration of salmon calcitonin in positively charged gelatin microspheres with particle sizes of 3.4 and 11.2 μm was approximately 50%.
In conclusion, the gelatin microspheres have been shown to be a useful vehicle for pulmonary delivery of salmon calcitonin.
Preclinical Study of an Oral Controlled Release Naltrexone Complex in Mice
Authors: Alvarez-Fuentes J , Rojas-Corrales M O , Holgado M A , Caraballo I , Micó J A , Fernández-Arévalo M 
Published: October 2002

Abstract
Naltrexone, a long-acting, orally effective, opioid antagonist which blocks opioid effects as well as the development of physical dependence, would appear to be a drug ideally suited to addiction treatment. An optimal dosage regimen is critical for the treatment patient compliance in ambulatory opiate detoxification programs. The ideal dosage regimen would be an oral controlled-release system of naltrexone that allowed once-a-day administration providing stable plasma levels.
A naltrexone-Eudragit L complex was produced in aqueous medium from naltrexone hydrochloride solution and Eudragit L30D (30% w/v) previously diluted (6% w/v) and partially neutralized. The antagonistic activity of naltrexone-Eudragit L on morphine-induced thermal antinociception, in comparison with conventional naltrexone, was evaluated, using the mouse hot-plate model. Mice were administered 10 mg kg−1 morphine subcutaneously, 10 min before test, and the antagonist products, either naltrexone-Eudragit L or naltrexone hydrochloride, were administered orally at 0.5, 1, 2, 4, 6, 8, 10, 12, 14 and 16 h before the test.
The results showed that the antagonism induced by naltrexone-Eudragit L was effective until 12 h after drug administration, while that induced by naltrexone hydrochloride disappeared 10 h after its administration. A 23.47% increase of the area under curve was obtained when naltrexone-Eudragit L was administered, compared with that induced by conventional naltrexone. The time taken to decrease the inhibition of analgesic activity to 50% was delayed by 51.80%.
This complexation technique can be considered as a useful tool in the design of oral controlled-release systems capable of inducing a long-lasting effect in-vivo.
Tocolytic Effects of a Long-acting β2-Adrenoceptor Agonist, Formoterol, in Rats
Authors: Shinkai Norihiro , Takayama Satoshi 
Published: October 2002

Abstract
We have assessed the tocolytic activity of formoterol, a novel long-acting and potent β2-adrenoceptor agonist, through its production of cyclic adenosine monophosphate, in comparison with ritodrine, a β2-adrenoceptor agonist used clinically to counter premature delivery.
Formoterol and ritodrine inhibited the amplitude and frequency of rat uterine contraction, with IC50 values of 3.8 times 10−10 and 4.7 times 10−7 M, respectively. Intravenous administration of formoterol or ritodrine caused inhibition of uterine motility and increased heart rate in a dose-dependent manner. Inhibition of uterine motility by oral administration of formoterol (0.3 and 1 mg kg−1) continued for at least 60 min, whereas that with ritodrine (100 mg kg−1) persisted for 15 min with rapid recovery thereafter in pregnant rats. The β-adrenoceptor binding of [125I]iodopindolol to the myometrium of pregnant rats was competitive with formoterol and ritodrine, with Ki values of 0.04 and 6.10 nM, respectively. Formoterol (10−6 — 10−4 M) and ritodrine (10−6 — 10−4 M) increased the level of cyclic adenosine monophosphate in lymphocytes in a dose-dependent manner.
The results suggested that formoterol caused relaxation of uterine motility through production of cyclic adenosine monophosphate. Thus, formoterol may be useful as a treatment to counter premature delivery.
The Anxiolytic Effect of Two Oriental Herbal Drugs in Japan Attributed to Honokiol from Magnolia Bark
Authors: Kuribara Hisashi , Kishi Eiko , Hattori Naoko , Okada Minoru , Maruyama Yuji 
Published: October 2002

Abstract
An improved elevated plus-maze test in mice revealed that seven daily treatments with two differnt traditional Chinese medicines, known as Kampo medicines in Japan, Hange-koboku-to (composed of extracts of 5 plants) and Saiboku-to (composed of extracts of 10 plants), produced an anxiolytic effect, and the effect was mainly due to the presence of honokiol derived from magnolia. This study was carried out to evaluate the anxiolytic potential of honokiol, Hange-koboku-to and Saiboku-to, which were prescribed with two different magnolia samples: Kara-koboku (Magnoliae officinalis) (KA) or Wa-koboku (Magnoliae obovata) (WA).
The doses of test samples were adjusted to ensure a constant dose of honokiol at 0.2 mg kg−1. Although the doses of magnolol (an isomer of honokiol), as well as those of undetermined chemicals, varied among samples, the seven daily treatments with 9 out of 10 test samples produced an anxiolytic effect almost equivalent to that produced by 0.2 mg kg−1 honokiol. The only exception was the sample containing the lowest amount of honokiol. Magnolia-free preparations of Hange-koboku-to or Saiboku-to did not have any anxiolytic effect.
These results confirm that honokiol derived from magnolia is the causal chemical of the anxiolytic effect of Hange-koboku-to and Saiboku-to.
In-vivo Drug Delivery of 5-Fluorouracil using Poly(2-hydroxyethyl methacrylate-co-acrylamide) Hydrogels
Authors: Blanco M D , Garcia O , Gomez C , Sastre R L , Teijon J M 
Published: October 2002

Abstract
Poly(2-hydroxyethyl methacrylate-co-acrylamide) hydrogels crosslinked with ethylen glycol dimethacrylate were used as devices for the in-vivo drug release of 5-fluorouracil (5-FU).
Drug-loaded hydrogels were subcutaneously implanted in the back of Wistar rats. All hydrogel discs reached an equilibrium swelling degree, which was slightly larger than that determined in-vitro. After 30 days of implantation, the hydrogel discs were transparent, and without fracture or apparent degradation. In addition, a fibrous capsule was not detected around the hydrogels that had greater hydration degrees. Release of 5-FU from these hydrogels allows the drug to remain in the plasma from 1 to 5 days, in spite of its short plasma half-life (15 min). This was an improvement of up to 98-times compared with the intraperitoneal drug administration.
Administration of 5-FU by implantation of 2-hydroxyethylmethacrylate-co-acrylamide copolymeric hydrogels seems to be a good candidate for 5-FU therapy, since the drug released results in a therapeutically suitable plasma concentration of 5-FU for an extended period of time, despite the short half-life of the drug.
Gastrointestinal First-pass Effect of Furosemide in Rats
Authors: Kim Eun Jung , Han Kye Soo , Lee Myung Gull 
Published: October 2002

Abstract
The first-pass effect of furosemide was investigated in rats. Furosemide intravenous solution (20 mgkg−1 Lasix), was administered via the jugular vein and the portal vein, orally, and instilled directly into the duodenum of rats. The first-pass effects of furosemide by lung, heart, and liver seemed to be negligible in rats. The absolute bioavailability of furosemide was 28.9 and 48.3% after oral and intraduodenal administration, respectively. Based on the gastrointestinal (GI) recovery study, 68.3 and 69.5% of furosemide were found to have disappeared mainly due to absorption and/or metabolism from rat GI tract after oral and intraduodenal administration, respectively.
The results indicate that gastrointestinal and intestinal first-pass effects of furosemide were approximately 40% (68.3–28.9%) and 20% (69.5–48.3%) of the dose, respectively.
Determination of the Salivary Retention of Hexetidine In-vivo by High-performance Liquid Chromatography
Authors: McCoy Colin P , Jones David S , McGovern James G , Gorman Sean P , Woolfson A David 
Published: October 2002

Abstract
The non-antibiotic antimicrobial agent hexetidine is widely used at a concentration of 0–1% w/v as an oral rinse to reduce the number of viable microorganisms within the oral cavity. However, following use, the available concentration of hexetidine in the oral cavity declines with time, thus compromising the resultant antimicrobial activity. It is, therefore, desirable to determine the persistence of the agent in the oral cavity by quantification of the drug concentration in saliva, thus enabling prediction of its antimicrobial activity in the oral environment.
A rapid reverse-phase HPLC method was therefore developed and validated for hexetidine in aqueous solution (Oraldene) and in saliva samples collected from volunteers post-rinsing with 15 mL of hexetidine oral rinse for 30 s. The HPLC assay was sufficiently sensitive to accurately detect hexetidine in saliva up to 25 min after in-vivo use of a commercial oral rinse. Furthermore, it was possible to detect hexetidine below the published minimum inhibitory concentrations (MICs) for a selection of microorganisms. From these data a first-order elimination rate constant of hexetidine from the oral cavity was determined post-rinsing in each of six volunteers.
The validated HPLC assay method presented is useful for the assay of hexetidine in the oral cavity both at and below MICs. The first-order elimination rate constant shows significant variation between volunteers.
Effects of Ba2+ on SK&F 96365-sensitive Sustained Contraction of Rat Pulmonary Artery
Authors: Uchida Kohsuke , Saito Kyoko , Kitajima Toshimitsu , Kamikawa Yuichiro 
Published: October 2002

Abstract
The effects of Ba2+ on receptor-mediated sustained contraction of rat pulmonary artery and guinea-pig oesophageal muscularis mucosae were studied in-vitro.
In rat isolated pulmonary artery, sustained contraction induced by noradrenaline (1 μm) was resistant to nicardipine (1 μm), but this same sustained contraction was completely inhibited by SK&F 96365 (30 μm), a blocker of voltage-dependent L-type Ca2+ channels and receptor-activated Ca2+ influx. The SK&F 96365-sensitive sustained contraction induced by noradrenaline (1 μM) may be due primarily to Ca2+ influx through receptor-activated Ca2+ channels resistant to nicardipine. Cumulatively applied BaCl2 (0.1 — 10 mM) increased the noradrenaline (1 μM)-induced sustained contraction of the pulmonary arterial preparation in the absence of nicardipine, but in the presence of nicardipine (1 μM), BaCl2 (0.1 — 3 mM) did not affect this contraction. A higher concentration of BaCl2 (10 mM), however, weakly inhibited the noradrenaline (1 μM)-induced tone. In addition, BaCl2 (3–10 mM) increased the tone induced by KCl (60 mM), and the BaCl2-elevated KCl tone was markedly inhibited by nicardipine (1 μM) treatment.
In the guinea-pig isolated oesophageal muscularis mucosae, sustained contraction induced by acetylcholine (3 μM) was resistant to nicardipine (1 μM) but was returned to its basal level by SK&F 96365 (30–60 μM). The SK&F 96365-sensitive, acetylcholine-induced sustained contraction of the oesophageal muscularis mucosae is also likely to link with receptor-activated Ca2+ channels resistant to nicardipine. In contrast to the rat pulmonary artery, cumulatively applied BaCl2 (0.3–10 mM) inhibited the acetylcholine (3 μM)-induced sustained contraction of the oesophageal muscularis mucosae in a concentration-dependent manner in the presence of nicardipine (1 μM).
In conclusion, Ba2+ presumably activates voltage-dependent Ca2+ channels by depolarizing plasma membrane and also passes through voltage-dependent Ca2+ channels to contract the pulmonary artery in the absence of nicardipine, and Ba2+ also has a minor effect on the nicardipine-resistant, SK&F 96365-sensitive sustained contraction induced by noradrenaline in rat isolated pulmonary artery.
Electron-microscopic Study of the Bactericidal Effect of OPB-2045, a New Disinfectant Produced from Biguanide Group Compounds, Against Methicillin-resistant Staphylococcus aureus
Authors: Sakagami Yoshikazu , Kajimura Keiji , Nishimura Hiroshi 
Published: October 2002

Abstract
The bactericidal effect of OPB-2045, a new disinfectant produced from biguanide group compounds, against methicillin-resistant Staphylococcus aureus (MRSA), MRSA IID 1677, was investigated by transmission electron microscopy.
OPB-2045 showed strong bactericidal activity against MRSA. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of OPB-2045 against the test strain were 0.78 and 1.56 μg mL−1, respectively. The test bacteria were incubated in the presence of OPB-2045 at 1/2 MIC (0.39 μg mL−1), 1 MIC (0.78 μg mL−1), 2 MIC (1 MBC, 1.56 μg mL−1), 4 MIC (2 MBC, 3.13 μg mL−1) or 10 MIC (5 MBC, 7.8 μg mL−1) at 37°C for 30 s, 3 min, 30 min or 6h. The morphology of the cells was examined by transmission electron microscopy.
The cell damage observed after 30-min or 6-h incubation in the presence of OPB-2045 at 1/2 or 1 MIC was the same as that at 2, 4 or 10 MIC. The numbers of damaged MRSA cells increased according to the increase in concentration of added disinfectant, and the image of bacteriolysis was observed, too.
After treatment at 1/2 or 1 MIC, a few leaking cells were recognized, but no destroyed cells were found. No morphological changes were observed after treatment at 1 or 2 MIC for 30 s, 3 min or 30 min. When the incubation time was extended to 6 h, morphological changes in the MRSA cells treated at 1 or 2 MIC were observed.
When examining the relationship between the numbers of surviving bacteria and the MIC (MBC) values in soybean casein digest broth, no decrease in MRSA cell numbers was recognized in the untreated control or at 1/2 MIC, but a marked decrease in MRSA cell numbers was recognized as the OPB-2045 concentration was increased.
The new disinfectant OPB-2045 would make a useful contribution to the medical field for the prevention of infections caused by pathogenic bacteria such as MRSA.
Balicalin, the Predominant Flavone Glucuronide of Scutellariae Radix, is Absorbed from the Rat Gastrointestinal Tract as the Aglycone and Restored to its Original Form
Authors: Akao Teruaki , Kawabata Kiyoshi , Yanagisawa Erika , Ishihara Kazuhisa , Mizuhara Yasuharu , Wakui Yoko , Sakashita Yoko , Kobashi Kyoichi 
Published: October 2002

Abstract
When baicalin was orally administered to conventional rats, it was detected in their plasma for 24 h after administration, but baicalein, the aglycone of baicalin, was not detected. However, when baicalin was given to germ-free rats, only a small amount of baicalin was detected in their plasma within 2 h after the administration, its AUC0-lim (the area under the concentration-time curve from 0 to last determination time) being 12.0% of that in conventional rats. Subsequently, a considerable amount (55.1 ± 6.2%) of baicalin was recovered from the gastrointestinal tract even 4 h after administration. When baicalein was orally administered to conventional rats, however, baicalin appeared rapidly in their plasma at an AUC0-lim value similar to that obtained after oral administration of baicalin, despite the absence of baicalein in plasma. When intestinal absorption was evaluated by the rat jejunal loop method, baicalein was absorbed readily, but only traces of baicalin were absorbed. Moreover, in conventional rats a small amount (13.4 ± 3.1%) of baicalin and an appreciable amount (21.9 ± 3.4%) of baicalein were recovered from the gastrointestinal tract even 4 h after oral administration of baicalin, but only a small amount (3.93 ± 1.43%) of baicalein was detected in the intestinal tract 1 h after administration of baicalein.
Baicalin was transformed to baicalein readily by the rat gastric and caecal contents. When baicalin was administered orally to conventional rats, an appreciable amount of baicalein was recovered in their gastrointestinal tracts. Moreover, baicalein was efficiently conjugated to baicalin in rat intestinal and hepatic microsomes.
These results indicate that baicalin itself is poorly absorbed from the rat gut, but is hydrolysed to baicalein by intestinal bacteria and then restored to its original form from the absorbed baicalein in the body.
Transdermal Delivery of the Potent Analgesic Dihydroetorphine: Kinetic Analysis of Skin Permeation and Analgesic Effect in the Hairless Rat
Authors: Ohmori Satoshi , Hayashi Teruaki , Kawase Masami , Saito Setsuo , Sugibayashi Kenji , Morimoto Yasunori 
Published: October 2002

Abstract
Dihydroetorphine is an extraordinarily strong opioid analgesic. To assess its effectiveness after topical application in hairless rats we have examined the kinetic analysis of skin permeation through excised skin and the in-vitro reservoir effect of skin, and have investigated the predictability of plasma concentration and analgesic effect following in-vivo transdermal application.
Dihydroetorphine was moderately permeable from an aqueous suspension through excised hairless rat skin. Dihydroetorphine flux from drug-dispersed pressure-sensitive adhesive tape was threefold that from the applied aqueous suspension. The fluxes through the abdominal and the dorsal skin during tape application fitted the Fickian diffusion equation well after the tape was removed peeling off the outer layer of the stratum corneum. The relationship between the plasma concentration and the analgesic effect was examined for four different rates of infusion of dihydroetorphine. A non-linear pharmacokinetic disposition was observed. Following abdominal (0.28 cm2, 20μg) and dorsal (0.50 cm2, 35μg) applications of the dihydroetorphine tape, plasma concentration (0.2-0.8 ng mL−1) and analgesic effect were maintained at a suitable level, for more than 8h, until removal of the tape. These profiles were predictable using the combined equation for percutaneous absorption, disposition and the analgesic effect, but the analgesic effect was slightly lower than the predicted value.
The results show that it was possible to control the plasma concentration and the analgesic effect of dihydroetorphine by topical application of the analgesic using pressure-sensitive adhesive tape in the hairless rat. It was possible to predict the result using mathematical modelling.
Different Effects of Amitriptyline and Imipramine on the Pharmacokinetics and Metabolism of Perazine in Rats
Authors: Daniel Wladyslawa A , Syrek Maciej , Haduch Anna , Wójcikowski Jacek 
Published: October 2002

Abstract
The aim of this study was to search for possible effects of imipramine and amitriptyline on the pharmacokinetics and metabolism of perazine at steady state in rats. Perazine (10 mg kg−1, i.p.) was administered to rats twice daily for two weeks, alone or jointly with imipramine or amitriptyline (10 mg kg−1 i.p.). Concentrations of perazine and its two main metabolites (5-sulphoxide and N-desmethylperazine) in the plasma and brain were measured at 30 min (Cmax), 6h and 12h (slow disposition phase) after the last dose of the drugs. Liver microsomes were prepared 24 h after withdrawal of the drugs.
Amitriptyline increased the plasma and brain concentrations of perazine (up to 300% of the control) and N-desmethylperazine, while not affecting those of 5-sulphoxide. Imipramine only tended to increase the neuroleptic concentration in the plasma and brain. Studies with control liver microsomes showed that amitriptyline and imipramine added to the incubation mixture in-vitro, competitively inhibited N-demethylation (Ki (inhibition constant) = 16 μM and 164 μM, respectively) and 5-sulphoxidation (Ki = 57 μM and 86 μM, respectively) of perazine, amitriptyline being a more potent inhibitor of perazine metabolism, especially with respect to N-demethylation. Studies with microsomes of rats treated chronically with perazine or tricyclic antidepressants, or both, did not show significant differences in the rate of perazine metabolism between perazine- and perazine+antidepressant-treated rats. The data obtained were compared with the results of analogous experiments with promazine and thioridazine.
It was concluded that elevations of perazine concentration were caused by direct inhibition of the neuroleptic metabolism by the antidepressants. Similar interactions, possibly leading to exacerbation of the pharmacological action of perazine, may be expected in man. Since the interactions between phenothiazines and tricyclic antidepressants may proceed in two directions, reduced doses of both the neuroleptic and the antidepressant are recommended when the drugs are administered jointly.