bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapeutic Value of Ginkgo biloba in Reducing Symptoms of Decline in Mental Function
Authors: Curtis-Prior Peter , Vere Duncan , Fray Paul 
Published: July 2003

Abstract
The Chinese tree Ginkgo biloba or “maiden hair tree” is extensively cultivated for the exploitation of the medicinal properties of its leaves. From these, a well-defined extract designated “EGb 761” has been developed, which was commercialized initially as Tanakan, Tebonin and Rokin; a similar product, Kaveri (LI 3170), also exists. The major therapeutic applications for these products are “cerebral insufficiency”, other cerebral disorders, neurosensory problems and peripheral circulatory disturbances. Four primary concepts of action have been proposed to explain the pharmacotherapeutic benefits of EGb761; these are: vasoregulatory, cognition-enhancing, stress-alleviating, and gene-regulatory. These actions are believed to be realized through the principal active ingredients, flavonoids and the terpenoids ginkgolides and bilobalide acting simultaneously in concert, combination and synergy, so-called polyvalent action.
It has been proposed that EGb761 may improve the memory of healthy volunteers, and in an assessment meta-analysis of forty clinical studies, it was reported that Ginkgo was able to improve the twelve different symptoms comprising ‘cerebral insufficiency’, all of which are manifest in the elderly. These were supported in a second major study, using LI1370. However, in both instances, the evidence was largely based upon the results of self-assessment questionnaires. Latterly, in a large double blind study of men and women with the diagnosis of uncomplicated dementia who were administered Ginkgo for a year, a further positive outcome was claimed. In this study, patients were tested using ADAS-cog, GERRI and CGIC.
It is suggested that whilst these different outcomes are compatible with (but do not affirm) a clinical benefit resulting from the use of Ginkgo, the application of a more objective system of assessment would be able to provide firm proof. It is proposed, therefore, that an objective, computer-based testing system for assessment of clinical improvement in volunteers and patients administered Ginkgo (such as CANTAB) would provide the convincing evidence currently being sought by patients, carers, physicians, legislators and the pharmaceutical industry.
Synthesis and Cytotoxicity Evaluation of Some 8-Hydroxyquinoline Derivatives
Authors: Shen Ai-Yu , Wu Sheng-Nan , Chiu Chih-Tsao 
Published: July 2003

Abstract
Interest in Mannich bases of 8-hydroxyquinoline stems from reports of their high potency against human cancer cells. In the search for potential anticancer drug candidates, Mannich bases of 8-hydroxyquinoline (7-pyrrolidinomethyl-8-hydroxyquinoline, 7-morpholinomethyl-8-hydroxyquinoline, 7-piperidinomethyl-8-hydroxyquinoline and 7-diethylamino-methyl-8-hydroxyquinoline) were synthesised by reaction with various secondary amines and formaldehyde. They were prepared as hydrochlorides.
The cytotoxic activity of 7-pyrrolidinomethyl-8-hydroxyquinoline, 7-morpholinomethyl-8-hydroxyquinoline and 7-diethylaminomethyl-8-hydroxyquinoline compounds in the National Cancer Institute in-vitro cancer cell line panel was determined. It was found that they exhibited substantial cytotoxic activity against leukaemia. The log concentration of 7-pyrrolidinomethyl-8-hydroxyquinoline, 7-morpholinomethyl-8-hydroxyquinoline and 7-diethylaminomethyl-8-hydroxyquinoline that inhibited 50% of 60 cell lines' growth were —4·81M, —5·09M and —5·35M, respectively. Compound 7-pyrrolidinomethyl-8-hydroxyquinoline was selected for further in-vivo testing. The electrophysiological effect of 7-pyrrolidinomethyl-8-hydroxyquinoline also was tested in human myeloma cells (RPMI 8226). The outward current was voltage dependent, activating at —40 mV and believed to be the voltage-activated K+ current IK(V). 7-Pyrrolidinomethyl-8-hydroxy-quinoline (1–30 μM) caused the inhibition of IK(V) in a concentration-dependent manner. The IC50 value of 7-pyrrolidinomethyl-8-hydroxyquinoline-induced inhibition of IK(V) is 23 μM. The GI50 value of 7-pyrrolidinomethyl-8-hydroxyquinoline-induced inhibition of cell growth is 14 μM.
The results suggest that at least part of the cytotoxicity effect of 7-pyrrolidinomethyl-8-hydroxyquinoline on myeloma cells could be related to blockade of voltage-activated K+ channels.
Synthesis and Anticonvulsant Activity of N-Benzyloxycarbonyl-Amino Acid Prodrugs of Phenytoin
Authors: Scriba Gerhard K E , Lambert Didier M 
Published: July 2003

Abstract
Glycine, which has weak anticonvulsant properties, has been shown to potentiate the activity of several antiepileptic drugs but not phenytoin. Recently, studies have shown that N-(benzyloxycarbonyl)glycine (Z-glycine) antagonized seizures more than glycine in addition to possessing activity in the maximal electroshock test, a convulsive model in which glycine is inactive. In the present study esters of 3-hydroxymethylphenytoin, a phenytoin prodrug, and Z-glycine as well as the homologous N-(benzyloxycarbonyl)-ω-amino acids, Z-β-alanine and Z-σ-aminobutyric acid (Z-GABA), were prepared and tested for their anticonvulsant and acute neurotoxic activities.
The phenytoin prodrugs were obtained by esterification of bis(2-oxo-3-oxazolidinyl)-phosphinic acid chloride-mediated esterification of 3-hydroxymethylphenytoin with the respective N-benzyloxycarbonyl-protected amino acid. The Z-glycine-phenytoin ester was the most active anticonvulsant derivative. Compared with phenytoin the compound exhibited a decreased median effective dose (ED50) in the MES test and an increased median toxic dose (TD50), resulting in an significantly improved protective index expressed as the ratio between TD50 and ED50.
The present data suggest that covalent binding of phenytoin to Z-glycine results in an improved pharmacological profile of the drug.
Vascular-selective Effect of Lercanidipine and other 1,4-Dihydropyridines in Isolated Rabbit Tissues
Authors: Angelico P , Guarneri L , Leonardi A , Testa R 
Published: July 2003

Abstract
The aim of this study was to characterize the in-vitro vasoselectivity of lercanidipine (in comparison with lacidipine, amlodipine, nitrendipine and felodipine) by evaluating its functional calcium antagonistic activity on rabbit vascular (aorta) and cardiac tissues (heart ventricle).
Although incubation with all the compounds tested elicited a concentration-dependent relaxant effect on vascular tissue precontracted with KCl (80 mM), 50% relaxation was reached at different times for each concentration and drug tested. At 10 nM concentration 50% relaxation was reached after 210 min with lercanidipine, 278 min with amlodipine, 135 min with lacidipine, 75 min with nitrendipine and 70 min with felodipine. The onset of the effect was, therefore, similar for lercanidipine, amlodipine and lacidipine, but faster for nitrendipine and felodipine. Similarly, all the compounds tested concentration-dependently reduced the force of cardiac contraction (negative inotropic activity). In this model, the time needed to reach 50% reduction in contractile force was also concentration-dependent, and the ranking order of the speed of onset of the effect (evaluated as the ratio of the IC50 values (the concentrations inhibiting contraction by 50%) calculated after 1 and 4h incubation) was lacidipine (3.8) &gt; amlodipine (9.6) &gt; felodipine (39) &gt; lercanidipine (68) = nitrendipine (89). The vasoselectivity, expressed as the ratio of the IC50 values obtained on cardiac and vascular tissue, were (for 4 h incubation) 730, 193, 95, 6 and 3 for lercanidipine, lacidipine, amlodipine, felodipine and nitrendipine, respectively, showing that lercanidipine is the most vasoselective of the calcium-antagonists tested.
The results show that lercanidipine reduces the inotropic force of the rabbit heart to a lesser extent than do other calcium antagonists, and that this drug had the best heart/vessel selectivity index among the compounds tested at all the times tested.
Evaluation of the Protective Effects of Alkaloids Isolated from the Hooks and Stems of Uncaria sinensis on Glutamate-induced Neuronal Death in Cultured Cerebellar Granule Cells from Rats
Authors: Shimada Yutaka , Goto Hirozo , Itoh Takashi , Sakakibara Iwao , Kubo Masayoshi , Sasaki Hiroshi , Terasawa Katsutoshi 
Published: July 2003

Abstract
We have previously shown that an aqueous extract of the hooks and stems of Uncaria sinensis (Oliv.) Havil., Uncariae Uncus Cum Ramulusis, protects against glutamate-induced neuronal death in cultured cerebellar granule cells by inhibition of Ca2+ influx. Because it is not known which components of Uncaria sinensis are active, in this study we have evaluated, by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) staining, the neuroprotective effects of the oxyindole alkaloids corynoxeine, rhynchophylline, isorhynchophylline and isocorynoxeine, and the indole alkaloids geissoschizine methyl ether, hirsuteine and hirsutine, isolated from the hooks and stems of Uncaria sinensis, on glutamate-induced cell death. We also investigated the inhibitory effects of the compounds on 45Ca2+ influx in cultured rat cerebellar granule cells.
Cell viability evaluated by the MTT assay was significantly increased by application of rhynchophylline (10−3M), isorhynchophylline (10−4-10−3M), isocorynoxeine (10−4-10−3M), hirsuteine (10−4-3 × 10−4M) or hirsutine (10−4-3 × 10−4M) compared with exposure to glutamate only, with the effect of isorhynchophylline being the strongest. The increased 45Ca2+ influx into cells induced by glutamate was significantly inhibited by administration of rhynchophylline (10−3M), isorhynchophylline (3 × 10−4-10−3M), isocorynoxeine (3 × 10−4-10−3M), geissoschizine methyl ether (10−3M), hirsuteine (3 × 10−4-10−3M) or hirsutine (3 × 10−4-10−3M).
These results suggest that oxyindole alkaloids such as isorhynchophylline, isocorynoxeine and rhynchophylline and indole alkaloids such as hirsuteine and hirsutine are the active components of the hooks and stems of Uncaria sinensis which protect against glutamate-induced neuronal death in cultured cerebellar granule cells by inhibition of Ca2+ influx.
Effects of Hypericum perforatum on Levels of 5-Hydroxytryptamine, Noradrenaline and Dopamine in the Cortex, Diencephalon and Brainstem of the Rat
Authors: Calapai G , Crupi A , Firenzuoli F , Costantino G , Inferrera G , Campo G M , Caputi A P 
Published: July 2003

Abstract
The plant Hypericum perforatum is used in folk medicine to treat several diseases and research attention has been recently focused on its antidepressant action. Hypericin and flavonoids are the most important constituents of the plant, but the exact role of these compounds in the effects of hypericum on mood disorders is not well known. We have investigated the contribution of these compounds to the antidepressant effects of hypericum.
The effects of acute administration of hypericum extracts on levels of 5-hydroxytryptamine (5-HT), tryptophan, 5-hydroxyindoleacetic acid (5-HIAA), noradrenaline and dopamine in the cortex, diencephalon and brainstem was evaluated. The levels of these neurotransmitters were measured 1 h and 24 h after administration of two different extracts, one containing 0.3% hypericin and 6% flavonoids (Li 160; 25–500 mg kg−1), the other containing 0.3% hypericin and 50% flavonoids (Ph-50; 25–500 mg kg−1). Results from experiments performed on 5-HT turnover were compared with the effects of fluoxetine (10–80 mg kg−1). Li 160, Ph-50 and fluoxetine induced a significant increase in the 5-HT content of the cortex. In the diencephalon Ph-50, but not Li 160 or fluoxetine, elicited an increase in 5-HT and 5-HIAA levels. In the brainstem Ph-50 and fluoxetine caused an increase in 5-HT content; Li 160 did not change neurotransmitter content. Both Li 160 and Ph-50 caused increases of noradrenaline and dopamine in the diencephalon. In the brainstem only Ph-50 induced an increase in noradrenaline content.
Our data confirm that acute administration of hypericum extracts modifies the levels of neurotransmitters involved in the pathophysiology of mood disorders. When the extracts contain a higher concentration of flavonoids the effects are more widespread and involve brain regions such as diencephalon and brainstem that are implicated in depression.
Hepatoprotective Properties in the Rat of Mitracarpus scaber (Rubiaceae)
Authors: Germanò M P , Sanogo R , Costa C , Fulco R , D'Angelo V , Torre E A , Viscomi M G , De Pasquale R 
Published: July 2003

Abstract
The effect of Mitracarpus scaber on carbon tetrachloride-induced acute liver damage in the rat has been evaluated.
Results showed that treatment with Mitracarpus scaber decoction resulted in significant hepatoprotection against CCl4-induced liver injury both in-vivo and in-vitro. In-vivo, Mitracarpus scaber pretreatment reduced levels of serum glutamate-oxalate-transaminase (P &lt; 0.01 for 250, 500 and 1000 mg kg−1) and serum glutamate-pyruvate-transaminase (P &lt; 0.05 for 250 mg kg−1 and P &lt; 0.01 for 1000 mg kg−1) previously increased by administration of CCl4. In-vitro results indicated that addition to the culture medium of Mitracarpus scaber extracts significantly reduced glutamate-oxalate-transaminase (P &lt; 0.05 for 100 μg mL−1 and P &lt; 0.01 for 10 and 1000 μg mL−1) and lactate dehydrogenase activity (P &lt; 0.05 for 10 μg mL−1). Mitracarpus treatment also resulted in a good (&gt; 93%) survival rate for the CCl4-intoxicated hepatocytes as demonstrated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Moreover, as in the in-vitro assay, Mitracarpus scaber had radical-scavenging properties, shown by its reaction with the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical (EC50, the extract concentration resulting in a 50% reduction in the absorbance of DPPH blank solution, = 41.64 ± 1.5 μg mL−1).
The results of this study showed that Mitracarpus scaber had antihepatotoxic potential, a finding which supports the validity of traditional usage of this drug in Mali for the treatment of liver diseases.
Anti-ulcerogenic Mechanisms of a Lyophilized Aqueous Extract of Dalbergia monetaria L. in Rats, Mice and Guinea-pigs
Authors: Cota Ricardo H S , Grassi-Kassisse Dora M , Spadari-Bratfisch Regina C , Souza Brito Alba R M 
Published: July 2003

Abstract
The decoction of Dalbergia monetaria L. is popularly used in Brazil for the treatment of gastric ulcer and the lyophilized aqueous extract (LAE) of D. monetaria has significant anti-ulcerogenic activity and inhibits gastric ulcer lesions induced by pylorus-ligature, ethanol and hypothermic-restraint stress. This work was conducted to identify the anti-ulcerogenic mechanisms of action of the LAE of D. monetaria. We analysed the effect of the LAE on prostaglandin E2 (PGE2) synthesis and on the characteristics (pH, volume and total acid content) of gastric juice. The antagonism between the LAE and histamine or carbachol was also analysed.
The LAE increased gastric mucosal PGE2 synthesis compared with control (89.7 ± 21.5 and 52.6 ± 11.8 pg mg−1, respectively) as assayed by enzyme immunoassay in the rat stomach. The LAE reduced the total acid content of gastric juice, but did not modify pH or gastric volume significantly, in Shay rats. Dose-response curves to histamine were shifted to the right in guinea-pig isolated right atria (pD2 values were 5.77 ± 0.2 and 5.42 ± 0.3, respectively, in the absence and presence of the LAE), with a significant reduction in maximum response (140 ± 15.1 and 98 ± 13.0, respectively). The same effect was observed when the agonist was isoprenaline. The LAE had no effect on the dose-response curve to carbachol in rat fundus strips.
Thus, the protective effect of the LAE on induced gastric lesions might be because of synergistic effects, e.g. increased PGE2 synthesis and antagonism of H2 histamine and β-adrenergic receptors, reducing gastric acid secretion. Increased PGE2 synthesis results in increased protection, and antagonism of H2 histamine and β-adrenergic receptors reduces aggressive factors against the gastric mucosa.
Effect of Some Antidepressants on Glycaemia and Insulin Levels of Normoglycaemic and Alloxan-induced Hyperglycaemic Mice
Authors: Erenmemisoglu A , Ozdogan U K , Saraymen R , Tutus A 
Published: July 2003

Abstract
Depression is an important problem among diabetic patients. We have investigated the effect of some antidepressant drugs on plasma glucose and insulin levels in normoglycaemic and alloxan-induced diabetic mice. For this purpose the effects of nortryptiline (as an example of a tricyclic antidepressant) and fluoxetine and sertraline (as examples of selective 5-HT re-uptake inhibitors) were examined on plasma glucose and insulin levels.
Nortryptiline significantly increased glucose levels and reduced insulin levels in all animals. Although neither fluoxetine nor sertraline induced changes in insulin levels, both significantly reduced the blood glucose levels of mice.
These results suggest that antidepressive treatment has important risks particularly for diabetics. Tricyclic antidepressants might induce an important decrease in glucose tolerance and worsen the control of diabetic patients. Selective 5-HT re-uptake inhibitors, on the other hand, might reduce plasma glucose independently of insulin levels. This point is particularly important and should be remembered when insulin or oral antidiabetic agents are administered to diabetics, because of the possible risk of hypoglycaemia.
Influence of Dietary Iodine on Drug-induced Hypothyroidism in the Rat
Authors: Beyssen M L , Lagorce J F , Cledat D , Buxeraud J 
Published: July 2003

Abstract
Several compounds of pharmaceutical importance from a variety of chemical families, for example chlorpromazine and clomipramine, have been found to form charge-transfer complexes with iodine. We have investigated the influence of dietary iodine on thyroid-gland dysfunction induced by clomipramine, chlorpromazine or 2-thiazoline-2-thiol. We suggest that iodine is partly diverted from its metabolic pathway by complexation with drugs, and so the urinary concentration of iodide is increased.
Both chlorpromazine and clomipramine, at doses which do not inhibit thyroperoxidase, enhanced urinary iodine excretion when dietary iodine was restricted (3.94 ± 0.96 μg/day for chlorpromazine-tested rats, 3.43 ± 1.33 μg/day for clomipramine-tested rats, compared with 2.34 ± 0.11 μg/day in control rats). Concurrently, these pharmaceutical compounds increased the level of free thyroid-stimulating hormone (TSH) in comparison with controls and induced histological modifications in, and enlargement of, the thyroid gland.
We have demonstrated that drug-induced loss of iodine in the urine was associated with antithyroid action when iodine intake was limited.
Gelatin Behaviour in Dilute Aqueous Solution: Designing a Nanoparticulate Formulation
Authors: Farrugia Claude A , Groves Michael J 
Published: July 2003

Abstract
Although it has been claimed that nanoparticles can be produced from gelatin, a naturally occurring polypeptide, the commercial conversion of animal collagen to gelatin results in a heterogeneous product with a wide molecular-weight range. This is probably responsible for the widely observed variation in the experimental conditions required for nanoparticle formation.
In this study, 0.2% w/v aqueous B225 gelatin solutions were incubated under various conditions of time, temperature, pH and ethanol concentration and characterized by both size-exclusion high-performance liquid chromatography (HPLC) and dynamic light scattering. Gelatin was shown to be denatured when the temperature was increased to 37°C (approx.) and the rate of renaturation was optimized over the temperature range 7–20°Cat pH5.0, equivalent to the isoelectric point (IEP). The molecular-weight profile remained unchanged at 37°C (approx.) in the pH range 5–7. When the gelatin solutions were mixed with ethanol, higher-molecular-weight fractions (microgel, δ and ζ fractions, all with molecular weights &gt; 700 kDa) precipitated at ethanol concentrations lower than those required to precipitate the lower molecular weight material (&lt; 700 kDa), with maximum precipitation occurring close to the isoelectric point (pH 5.0).
The molecular weight profile of gelatin in solution is evidently critically affected in a time-dependent manner by both pH and temperature. These two factors influence the noncovalent interactions responsible for the molecular structure of gelatin. The molecular weight profiles, in turn, affect the phase behaviour of gelatin in hydroalcoholic solutions. Systematically investigating the effect of time, temperature, pH and ethanol concentration on the molecular-weight-distribution profile of a gelatin solution enabled a robust method to be developed for the preparation of colloidal dispersions of non-aggregated gelatin nanoparticles 220–250 nm in diameter. This contrasts with the multiparticulate aggregates produced by earlier literature methods.
Osmotic Behaviour of Polyhedral Non-ionic Surfactant Vesicles (Niosomes)
Authors: Arunothayanun Parinya , Uchegbu Ijeoma F , Florence Alexander T 
Published: July 2003

Abstract
In addition to common spherical non-ionic surfactant vesicles (niosomes), disc-like, tubular, and polyhedral niosomes have also been reported. The permeability and osmotic activity of niosomes are important in determining their use as controlled-release drug-delivery systems. These properties have been compared for polyhedral niosomes prepared by hydrating a mixture of a hexadecyl diglycerol ether (C16G2), a poly(24)oxyethylene cholesteryl ether (Solulan C24), 91: 9 or 98: 2, and conventional spherical niosomes prepared from the same surfactants but with cholesterol.
When subjected to osmotic gradients, polyhedral niosomes, the membranes of which are in the gel phase, swell and shrink less than their spherical counterparts and they are more permeable to the hydrophilic solute 5(6)-carboxyfluorescein. In 2 M NaCl the rate of release of carboxyfluorescein from polyhedral niosomes (both containing 9% Solulan C24) into either a hypotonic (water) or an isotonic medium (2 M NaCl) was low. This contrasted with similarly loaded spherical niosomes and polyhedral niosomes containing 2% Solulan C24, from which release was high in hypotonic media (e.g. water) but less in an isotonic medium (2 M NaCl). For both polyhedral and spherical niosomes encapsulating carboxyfluorescein (pKa = 6.4), release rates were higher at pH 8 than at pH 5.
Polyhedral niosomes are thus, in general, less osmotically active than spherical niosomes because of their rigid but highly permeable membranes. The unusual polyhedral membrane impermeability to carboxyfluorescein co-entrapped with salt in hypotonic media is a function of Solulan C24 content, and is possibly a result of salting out of the polyoxyethylene chains; this is, therefore, a property that might be manipulated in the design of a drug-delivery system.