bluuebunny/crossref_metadata_2025 huggingface dataset:
Purification and characterisation of large and small maitotoxins from cultured gambierdiscus toxicus
Authors: Holmes Michael J. , Lewis Richard J.
Published: October 2006

Three strains of cultured Gambierdiscus toxicus yielded distinct maitotoxins (maitotoxin‐1, ‐2, and ‐3) which were purified to homogeneity by high pressure liquid chromatography. Maitotoxins‐1 and ‐2 are large toxins (molecular weights for the sodium salts = 3,422 and 3,298, respectively), whereas maito‐toxin‐3 is relatively small (molecular weight = 1,060 for the sodium salt). The contractile actions on isolated guinea‐pig left atria, vas deferens and ilea of maitotoxins‐1 and ‐2 were compared with those of the small maitotoxin, maitotoxin‐3. Maitotoxin‐1, ‐2, and ‐3 each produced quantitatively similar, concentration‐dependent patterns of positive and negative inotropy in atria when compared on a mouse unit/ml basis (one mouse unit is the intraperitoneal LD50 dose for a 20 g mouse; the LD50 for maitotoxin‐2 = 0.08 μ g/kg). Concentrations of maitotoxin‐2 greater than 5 × 10−13 M caused positive inotropy. The three maitotoxins produced patterns of contractions in vas deferens and ilea that were qualitatively similar, including a period of prominent spike activity in vas deferens. On a mouse unit/ml basis, the order of potency on smooth muscle was maitotoxin‐1> maitotoxin‐3 > maitotoxin‐2. The contractile responses of smooth muscle to the maitotoxins were followed by an inhibitory phase where control agonist responses could not be elicited. The maitotoxin‐induced contractile responses of vas deferens were inhibited by nicardipine but not phentolamine, indicating that in this tissue, each maitotoxin has mainly a direct contractile effect that requires calcium influx through voltage‐sensitive calcium channels. The qualitatively similar in vitro (and in vivo) actions of the three toxins suggests that each maitotoxin has a similar mode of action, despite the considerable difference in their molecular size. The reduction in potency upon solvolysis of these maitotoxins suggests that sulphate moities are important for the biological activity of each maitotoxin. © 1994 wiley‐Liss, Inc.
Effects of low‐level dietary deoxynivalenol on haematological and clinical parameters of the pig
Authors: Prelusky Dan B. , Gerdes Robert G. , Underhill K. Lynne , Rotter Barbara A. , Jui Perry Y. , Trenholm H. Locksley
Published: October 2006

The subacute toxic effects of dietary deoxynivalenol (DON) were examined in grower pigs during a 32 day feeding period. DON was incorporated into the feed at 0,1, and 3 mg/kg, added as either the purified toxin (P) or as naturally contaminated corn (N). Growth performance and blood biochemical and haematological parameters were monitored throughout the study. At the higher toxin levels (diets 3P, 3N) significantly lower feed consumption and body weight gains were evident soon after the start of feeding, but while weight gains of pigs fed the pure DON diet (3P) recovered after several days, values for pigs fed the naturally contaminated diet (3N) remained depressed over the course of the study. It is possible that these observations reflected the presence of other unidentified toxic compounds in the naturally contaminated grain. Generally, blood chemistry parameters of pigs fed the contaminated diets were not different from controls, with the exception of α‐globulin and possibly cortisol in animals receiving diets 3N or 3P. Data suggested that the effect of DON on the a‐globulin fraction may have been independent of the feed refusal syndrome associated with this toxin. Alterations in several haematological measurements were noted to occur sporadically with the 3 ppm diets, including higher RBC count, haematocrit and platelet level, however these effects could not be separated from the influence of decreased feed intake and were of limited value in diagnosing the effects of low level dietary DON on swine. Published 1994 Wiley‐Liss, Inc.
Effects of pectenotoxin‐1 on liver cells in vitro
Authors: Zhou Zhen‐Hua , Komiyama Masatoshi , Terao Kiyoshi , Shimada Yutaka
Published: October 2006

The effects of pectenotoxin‐I (PTX1), a nondiarrheagenic toxin from mussels, on liver cells were investigated by fluorescence microscopy. The in vitro application of PTX1, to these cells induced reduction in number and loss in radial arrangement of microtubules. It also induced disruption of stress fibers and accumulation of actin at the cellular peripheries. Further studies are worthwhile to explore the feasibility of using PTX1, as a tool for analyzing the properties of cytoskeletal proteins. © wiley‐Liss, Inc.
Prevalence of exposure to aflatoxin and hepatitis B and C viruses in Guinea, West Africa
Authors: Diallo Mamadou S. , Sylla Abdoulaye , Sidibé Kaba , Sylla Bakary S. , Trepo Christian R. , Wild Christopher Paul
Published: October 2006

The prevalence of exposure to aflatoxin, hepatitis B virus (HBV), and hepatitis C virus (HCV), three important risk factors for hepatocellular carcinoma, was examined in Guinea, West Africa. A total of 75 sera were collected from men living in the Kindia region of lower Guinea. The sera were analysed by immunoassay of aflatoxin covalently bound to serum albumin as a marker of aflatoxin exposure. Over 90% of the sera contained detectable adduct levels, the hishest level being 385 pg aflatoxin B1‐lysine equivalent per mg albumin. Eleven subjects (14.7%) were positive for hepatitis B surface antigen in the serum and these subjects had a tendency to have higher aflatoxin‐albumin adduct levels than the other subjects (mean level 70.4 pg/mg compared to 44.1 pg/mg), but the difference was not statistically significant (P = 0.23). Eight subjects were positive for antibodies to HCV antigens and, interestingly, seven of these were from one ethnic group, Mandinka (25% prevalence). These data demonstrate that all three exposures are prevalent in Guinea and that the prevalence of these risk factors is comparable to that observed in other countries in West Africa. It is now important to assess the public health impact of these exposures in this country. © 1995 Wiley‐Liss, Inc.
microcystis aeruginosa: Behaviour and toxic features in San Roque Dam (Argentina)
Authors: Scarafia M. E. , Agnese A. M. , Cabrera J. L.
Published: October 2006

M. aeruginosa is a cyanophyte frequently found in the water at the San Roque Dam (raw water supply conditioned for human use in Córdoba city) that causes a bad smell and taste, as well as potential toxic hazards of a still unknown extent. A heavy bloom tested by mouse bioassay (i.p.) for the first time on January 27, 1989, revealed toxicity. The dominant cyanobacterial species in the water sample was M. aeruginosa. The lyophilized bloom material (LD50: 14.5 mg/kg body weight) and the toxin isolated (LD50 estimated: 500 μg/kg), when administered to mice i.p., induced clinical signs similar to those induced by peptide toxins produced by M. aeruginosa. HPLC detected toxin traces from a sample of drinking water collected on the same day as the bloom. A seasonal follow‐up was carried out for the next 4 years in order to compare bloom toxicity values during the most significant water blooms; these never yielded LD50 values lower than 200 mg liophilized bloom material/kg of mice. © 1995 Wiley‐Liss, Inc.
Effect of different inhibitors of sterol biosynthesis on both fungal growth and aflatoxin production
Authors: Fanelli Corrado , Fabbri Anna Adele , Brasini Stefano , De Luca Chiara , Passi Siro
Published: October 2006

Azole antifungals are reported to interfere with fungal growth by selective impairment of the P‐450 dependent 14 a‐demethylase system key to biosynthesis of ergosterol (ERG), thus leading to the depletion of this sterol in fungal membranes and to the accumulation of methylated precursors.

We have investigated whether azole antifungals ketoconazole, miconazole, econazole, or itraconazole were able to modify the sterol and fatty acid patterns of a toxigenic strain of Aspergillus parasiticus, inducing the growth of mycelium depleted of ergosterol (ERG) and rich in less oxidisable sterols. It had been demonstrated that oxidation of ERG is correlated to aflatoxin biosynthesis. However, in this study no alteration of sterol or fatty acid patterns was observed after 7, 14, and 21 days of incubation of A. parasiticus in the presence of sublethal doses of azole antifungals. Specific production of aflatoxin was unaffected.

Among the four antifungals tested, itraconazole was the strongest inhibitor of fungal growth and aflatoxin production while ketoconazole was the least effective. © 1995 Wiley‐Liss, Inc.
Induction of apoptosis by T‐2 toxin and other natural toxins in HL‐60 human promyelotic leukemia cells
Authors: Ueno Yoshio , Umemori Kiyoko , Niimi Eei‐Chi , Tanuma Sei‐Ichi , Nagata Satoshi , Sugamata Masao , Ihara Tomomi , Sekijima Masaru , Kawai Ken‐Ichi , Ueno Ikuko , Tashiro Fumio
Published: October 2006

Based on the DNA fragmentation profile in gel electrophoresis and the morphological changes in electron microscopy, the induction of apoptotic nuclear changes by mycotoxins and other microbial products, in total 31 chemicals, was investigated in HL‐60 human promyelotic leukemia cells, along with the cytotoxicity tests with 3‐[4,5‐dimethylthiazol‐zyl]‐2,5‐diphenyltetrazolium bromide (MTT) and trypan blue exclusion. Among the chemicals tested, trichothecenes (T‐2 toxin, roridin A, nivalenol, deoxynivalenol), certain anthraquinones (luteoskyrin, skyrin, 2‐hydroxyemodin), diketopiperazines (emethallicin A, emestrin), isocoumarins (ochratoxin A, citrinin), lactone (penicillic acid), dihydrobisfuran (aflatoxin B), potassium ionophore (valinomycin), and an inhibitor of interleukin‐2 synthesis (cyclosporin A) were positive for the induction of DNA fragmentation. No DNA fragmentation was observed under the present conditions with fumonisin B1, cyclic peptides (cyclochlorotine, phalloidin, microcystin‐LR), certain anthraquinones (emodin, chrysophanol, rugulosin), and others (sterigmatocystin, cytochalasin A, griseofulvin, fusaric acid, kojic acid, rubratoxin B, butenolide, wortmannin, FK506, and sphingosine). The apoptotic changes in the cells exposed to T‐2 toxin and luteoskyrin were confirmed by electron microscopic observation. Detailed experiments on dose and time dependencies revealed that T‐2 toxin induced the apoptosis at 10 ng/ml (= 4 × 10‐8 M) levels within 2‐6 hr without significant cytotoxicity evaluated by the dye exclusion and MTT. © 1995 Wiley‐Liss, Inc.
Fate of a single dose of 14C‐labelled fumonisin B1 in vervet monkeys
Authors: Shephard Gordon S. , Thiel Pieter G. , Sydenham Eric W. , Savard Marc E.
Published: October 2006

The mycotoxin fumonisin B1 (FB1) was dosed as 14C‐labelled FB1 to male vervet monkeys (Cercopithecus aethiops) both by intravenous (iv) injection (2 monkeys, dose 1.72 mg [86 kBq]/kg body weight) and by gavage (2 monkeys, dose 6.42 mg [321 kBq]/kg body weight). Excreta were collected over a 24‐hr period, whereafter the monkeys were sacrificed and selected organs and contents of the gut collected to determine the distribution of the 14C‐label. The bulk of the radioactivity recovered from tissue was found in the liver (mean of 1.92% in iv‐dosed monkeys; 0.64% in gavage‐dosed monkeys). Of the other organs analysed, the following mean amounts of radioactivity were recovered in organs of iv‐ and savage‐dosed monkeys, respectively: muscle, 0.62% and 0.14%; kidney, 0.37% and 0.03%; brain, 0.08% and 0.02%; lung, 0.07% and 0.03%; heart, 0.04% and 0.01%; spleen, 0.02% and < 0.01%; plasma, 0.66% and 0.12%; red blood cells, 0.11% and 0.01%; while a further 68.1% and 64.0% were recovered in excreta, bile, and the gut contents. Analysis of faeces and gut contents showed that radioactivity was due to FB1, its partially hydrolysed metabolites, and trace amounts of the fully hydrolysed aminopentol moiety. Analysis of bile showed an absence of hydrolysis products, indicating that hydrolysis occurred only in the gut, resulting in the removal of the tricarballylic acid moiety at the C14‐position. Determination of FB1 levels in plasma following a gavage dose indicated that only limited amounts of FB1 were absorbed, as plasma levels peaked after 1‐2 hr with levels below 210 ng/ml. © 1995 Wiley‐Liss, Inc.
Toxicity and metabolism of ochratoxin A
Authors: Fink‐Gremmels Johanna , Jahn Andrea , Blom Maarten J.
Published: October 2006

The frequent occurrence of ochratoxin A (OA) in food and feed commodities and the high incidence of human exposure, as confirmed by different surveillance studies initiated several investigations devoted to elucidating the molecular mechanisms underlying OA toxicity. Previous studies indicated that the primary effects of OA are the inhibition of tRNA synthetase, the inhibition of mitochondrial respiration, and a disturbance of intracellular calcium homeostasis inherent to lipid peroxidation processes. We here report the effect of OA on a number of toxicological endpoints including cytotoxicity in different cell lines and effects on macromolecular synthesis and cell proliferation in primary cultures of hepatocytes at concentrations corresponding to overall exposure levels. These studies provide evidence that prominent toxicological effects might be linked to biotransformation processes. Analysis of hepatic biotransformation resulted in the detection of a number of distinct stable OA‐metabolites. As metabolic activation has also been identified as an essential step in OA mutagenicity, the biological relevance on this mechanistic data is discussed. © 1995 Wiley‐Liss, Inc.
BCR‐ and M&T‐activities in the area of mycotoxin analysis in food and feedstuffs
Authors: Boenke Achim
Published: October 2006

In order to avoid undesirable side effects such as high contents of mycotoxins in food and feed, measurements at critical steps of the food and feed production chain are performed. These measurements need to be accurate and precise to satisfy these aims. The accuracy and precision requirements to measurements form the basis of the Bureau Communautaire de Référence (BCR)‐and Measurements and Testing (M&T)‐Projects. Such projects aim to improve and/or develop analytical methodology, sampling plans, to harmonise agreement of results between European Union Member States and to prepare suitable certified reference materials (CRMs). The selection of the matrix CRMs and their corresponding level of mycotoxin contamination is made on the basis of requirements of the applied analytical procedures, stability requirements, regulations, norms, and inter‐or intra‐trade agreements which are in relation to quality specifications of imported and/or exported goods. The availability of appropriate matrix CRMs is not only a prerequisite for the implementation of directives and norms. It allows the validation of new methods and provides a possible solution to trade disputes, means for the statistical control of analytical results, tools for laboratory accreditation, and it is the basis for harmonisation and traceability of proficiency schemes. © 1995 Wiley‐Liss, Inc.
Overview on community legislation in the field of official control of mycotoxins in feedingstuffs
Authors: Verardi Giuseppe , De Froidmont‐Görtz Isabelle
Published: October 2006

The Community legislation currently in force identifies a group of substances whose presence in feedingstuffs is undesirable. For each one of these substances, acceptable maximum levels have been fixed. The compliance with these levels in feedingstuffs must be checked by Community sampling and analysis methods. In the specific case of the aflatoxins, analytical methods, based on thin‐layer chromatography (TLC) and high performance liquid chromatography (HPLC), have been adopted by directive. Another directive has established a general sampling method. The practice, however, has shown that it is not applicable to very large batches where the distribution of the contaminants is not homogeneous. A small group of experts of the Commission reached the conclusion that in the future Community legislation, it will be appropriate: i) to divide the undesirable substances in two groups (substances with homogeneous and non‐homogeneous distribution); ii) to adopt two different strategies for the cargoes “at risk” and “not at risk”; iii) to have methods of sampling, preparation, and analysis which are fast, reliable, easy to apply, and recognized at the international level. These experts proposed adaptations in the directive on “Sampling,” in the case of large vessels, but suggested at the same time deferring any decision to the near future. © 1995 Wiley‐Liss, Inc.
Effects of microcystin‐lr on actin and the actin‐associated proteins α‐actinin and talin in hepatocytes
Authors: Ghosh Sushmita , Khan Safdar All , Wickstrom Mark , Beasley Val
Published: October 2006

Microcystin‐LR (MCLR) is a commonly encountered blue‐green algal hepatotoxin and a known inhibitor of cellular protein phosphatase types 1 and 2A. The toxin causes alterations in, and redistribution of, intermediate filaments, microtubules, and actin microfilaments (MFs) in affected cells. In this study, the effect of MCLR on the sequence of alterations in MFs and actin‐associated proteins (AAPs) of isolated hepatocytes was examined in an effort to determine whether morphologic changes induced in MFs by microcystins are a result of prior dislocation of AAPs. We studied the effects of MCLR exposure on α‐actinin and talin, two AAPs that play a role in the orientation of the MFs. Primary hepatocytes were incubated with 10 μM MCLR for 0‐64 min. The distribution of actin, α‐actinin, and talin were examined using fluorescence microscopy. MCLR induced similar changes in the distribution of actin and the AAPs. Actin filament redistribution was first observed after 12 min of MCLR exposure, and was characterized by detachment of MFs from the cell periphery, followed by condensation at distinct focal points and progressive collapse into the interior of affected cells. Changes in α‐actinin and talin distribution were first observed after 20 min of toxin exposure. The AAPs appeared to detach from focal contacts on the cytoplasmic surface of the plasma membrane, condense into cytoplasmic aggregates, and ultimately collapse into a juxtanuclear bundle. The results of this study indicate that, in hepatocytes exposed to MCLR, the collapse of actin MFs occurs prior to the dislocation of α‐actinin and talin. Changes in these actin associated proteins are not likely to account for the initial changes in actin MFs. © 1995 Wiley‐Liss, Inc.
Are terfenadine and astemizole non‐sedative antihistamine compounds? A meta‐analysis
Authors: Delargy P. , Po A. Li Wan
Published: October 2006

Objective: To assess the likelihood of astemizole and terfenadine inducing drowsiness compared with placebo in the light of recent reports that these antihistamines are not necessarily drowsiness‐free.

Method: Meta‐analysis was used to analyse data obtained from a search of the reports of trials of terfenadine, astemizole and chlorpheniramine. The latter was included as a positive control.

Results: Of the 284 trials screened, 229 were unsuitable for detailed analysis for various reasons, including use of concomitant medication, lack of pertinent information and duplicate publication. Fifty five trials contained the necessary details, 18 of these were cross‐over trials and 37 parallel group trials. Our analyses suggest that the design used had an effect on the incidence of drowsiness reported. Both astemizole and terfenadine were no more likely than placebo to induce drowsiness. The Mantel‐Haenszel pooled odds ratio (ORMH) and confidence interval (CI) for terfenadine were ORMH = 1.01; CI = [0.64, 1.57] for the parallel group trials. The astemizole data were too sparse for pooling with largely zero incidence rates. Chlorpheniramine was clearly sedative (ORMH = 4.07; CI = [2.25, 7.36] 95%).

In the cross‐over trials, none of the three antihistamines induced more drowsiness than a placebo, thus suggesting that such trials may mask potential subjective adverse effects.

Conclusion: Our results are consistent with the hypothesis that astemizole and terfenadine are essentially non‐sedative antihistamine compounds, while chlorpheniramine is sedative. Care should be exercised when evaluating potentially subjective adverse effects and trial design should be considered as a possible confounding factor.
Further validation of information recorded on a general practitioner based computerized data resource in the united kingdom
Authors: Jick Hershel , Terris Barbara Z. , Derby Laura E. , Jick Susan S.
Published: October 2006

Studies have been carried out to evaluate the quality and completeness of the data recorded by GPs on VAMP computers for the purpose of carrying out drug safety studies. In an earlier study of 58 practices we found that clinical diagnoses reflecting the diagnoses noted in the consultant letters were present on the computer 87% of the time. We have now evaluated a further 35 practices. Agreement between the information in the consultant letter and that on the computer was present in 121 of 126 (96%) instances.
Trinational case–control study of oral contraceptives and health
Authors: Spitzer Walter O. , Thorogood Margaret , Heinemann Lothar
Published: October 2006

The collaboration of Dr Neil Poulter and Professor Michael Marmot, both of the Department of Epidemiology and Public Health, University College London Medical School, was crucial for the preparation of the present research protocol. In particular, we made extensive use of a protocol prepared by Dr Poulter and Professor Marmot for the World Health Organization, entitled ‘WHO multicentre case–control study of cardiovascular disease and steroid hormone use’ during the feasibility study carried out in 1991.
Reporting of adverse drug reactions in relation to general medical admissions to a teaching hospital in Hong Kong
Authors: Chan Thomas Y. K. , Critchley Julian A. J. H.
Published: October 2006

In Hong Kong, adverse drug reactions (ADRs) are rarely reported. We tried to improve the reporting of ADRs in our medical unit at the Prince of Wales Hospital by promoting the scheme at our regular unit meetings and by including report forms at the time of admission in the case notes of all patients admitted to two general medical wards. Registrars and interns based in these wards were requested to report all ADRs by filling in standard report forms. The hospital records of these patients were then reviewed by one investigator with two aims: (1) to assess the proportions of ADRs being reported; (2) to determine how good junior staff are in reporting ADRs. During a 2‐month period in 1992, 430 patients were reviewed. A total of 122 ADRs were present in 98 patients either at the time of admission (n = 66) or after admission (n = 56), and of these, only six (5 per cent) were correctly reported. The diagnosis was either missed or wrong in 29 cases, which represent 24 per cent of the total number of ADRs. The remaining 71 per cent of ADRs were totally ignored. Possible ways to improve the reporting of ADRs in hospital are discussed.
Synthesis and photopolymerization of new dental monomers from o‐hydroxyaryl phosphonates
Authors: Sahin Gorkem , Albayrak Aylin Ziylan , Sarayli Zeynep , Avci Duygu
Published: October 2006

Novel aromatic mono‐ and diphosphonate monomers based on t‐butyl α‐bromomethacrylate were prepared for use in dental composites. The synthesis of the two monomers involved three steps: the reaction of diethyl phosphite with phenol or hydroquinone, the rearrangement of the resulting phosphate derivatives into o‐hydroxyaryl phosphonates with lithium diisopropylamide, and the reaction of o‐hydroxyaryl phosphonates with t‐butyl α‐bromomethacrylate. Then, the selective hydrolysis of the t‐butyl ester groups of the monomers with trifluoroacetic acid gave the other carboxylic acid containing monomers. The photopolymerization behaviors of the synthesized monomers with glycerol dimethacrylate and triethylene glycol dimethacrylate were investigated with photodifferential scanning calorimetry at 40 °C with 2,2′‐dimethoxy‐2‐phenyl acetophenone as the photoinitiator. The hydrolysis of the t‐butyl groups of the monomers increased the reactivity and the rates of polymerization of the monomers. The mixtures of the acid monomers showed rates of polymerizations similar to those of homopolymerizations of triethylene glycol dimethacrylate and glycerol dimethacrylate. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 6775–6781, 2006
Anti‐stress activity of sitoindosides VII and VIII, new acylsterylglucosides from Withania somnifera
Authors: Bhattacharya Salil K. , Goel Raj K. , Kaur Ravinder , Ghosal Shibnath
Published: October 2006

Two new acylsterylglucosides, sitoindoside VII and sitoindoside VIII, were isolated from the roots of Withania somnifera Dun., and were screened for putative anti‐stress activity because the plant is widely regarded as the ‘Indian Ginseng’ by practitioners of the traditional Indian system of medicine. Since an acceptable paradigm of pharmacological tests for anti‐stress screening has yet to be evolved, a battery of tests were employed to delineate the activity of the test compounds.

The total MeOH‐H2O (1:1) extractives of the roots of W. somnifera (SG‐1) and equimolecular combination of sitoindosides VII, VIII and withaferin‐A, a common withanolide, (SG‐2), exhibited significant anti‐stress activity in all the test parameters used. The two sitoindosides also produced per se anti‐stress activity, which was potentiated by withaferin‐A. A preliminary acute toxicity study indicated that the compounds have a low order of acute toxicity. The anti‐stress activity of SG‐1 and SG‐2 is consonant with the therapeutic use of W. somnifera in the Ayurveda, the Indian system of medicine.
Hypocholesterolaemic and hypotriglyceridaemic effects of subfractions from fenugreek seeds in alloxan diabetic dogs
Authors: Ribes G. , Da Costa C. , Loubatières‐Mariani M. M. , Sauvaire Y. , Baccou J. C.
Published: October 2006

The hypocholesterolaemic and hypotriglyceridaemic properties of fenugreek seed subfractions were studied in alloxan diabetic dogs. These subfractions were added to the diet of animals for 21 days. Subfraction a containing testa + endosperm (fibres 79.4%) induced a clear reduction in hyperglycaemia and in elevated plasma cholesterol levels. Subfraction b containing cotyledons + axis (proteins 52.8%, saponins 7.2%) caused a diminution in elevated plasma cholesterol and triglyceride levels. No beneficial effect was observed with subfraction P (proteins 70.50%). Subfraction S (saponins 22.2%) induced, like subfraction b, a reduction in hypercholesterolaemia and hypertriglyceridaemia of the diabetic dogs without inducing significant changes in HDL cholesterol concentrations. Our results show that the hypolipidaemic effects of fenugreek seeds are due to the fraction rich in fibres (hypocholesterolaemic effect) and to the fraction rich in saponins (hypocholesterolaemic and hypotriglyceridaemic effects).
Effects of baicalein on leukotriene C4 biosynthesis in human lymphocytes
Authors: Kimura Yoshiyuki , Okuda Hiromichi , Arichi Shigeru
Published: October 2006

Studies were made on the effects of baicalein (5,6,7‐trihydroxyflavone) on leukotriene C4 (LTC4) biosynthesis by calcium ionophore A 23187 in human lymphocytes. Baicalein inhibited calcium ionophore‐induced LTC4 biosynthesis in human lymphocytes. The concentration of baicalein required for 50% inhibition (IC50) of LTC4 formation was 4.3 × 10−7 M.
Spasmolytic activity of Thymus membranaceus essential oil
Authors: Zarzuelo A. , Navarro C. , Crespo M. E. , Ocete M. A. , Jiménez J. , Cabo J.
Published: October 2006

The spasmolytic activity of Thymus membranaceus essential oil in the duodenum isolated from rat has been investigated. The qualitative and quantitative composition of the essential oil was studied. The essential oil affects the duodenum in two ways, showing a spasmogenic action (due to 1,8‐cineole) and, on the other hand, an antagonistic non‐competitive effect against the contractions by acetylcholine (due to the phenols and hydrocarbons).
Antiarrhythmic and local anaesthetic actions of the anti‐ascaris fraction of the ethanolic extract of the bark of Polyadoa umbellata—Dalziel (erin‐yoruba)
Authors: Onuaguluchi G. , Ihekwaba A.
Published: October 2006

The anti‐ascaris fraction of the ethanolic extract of the bark of Polyadoa umbellata (erin) was shown to possess definite antiarrhythmic activity superior to that of lignocaine. Erin protected toads against death due to the minimum dose of ouabain which caused 100% mortality. The therapeutic indices for erin and lignocaine were 5.6 and 3.16 respectively. It was, however, not possible to achieve more than 60% protection with lignocaine and therefore the safety factor (SF) in respect of lignocaine could not be determined. The SF for erin was 0.7. Erin at 60 mg/kg (i.v.) caused BaCl‐induced ventricular dysrhythmia/tachycardia to revert to sinus rhythm in five out of ten rats. Lignocaine at 6 mg/kg (i.v.) achieved this in three out of ten rats. Although lignocaine was about ten times more potent than erin in this regard, it was found from acute toxicity studies in mice to be about 18 times more toxic than erin.

Using the guinea‐pig wheal preparation for the determination of the degree of infiltration anaesthesia, lignocaine was found to be about 22 times more potent than erin. However using the rabbit corneal reflex preparation, lignocaine was only 4.5 times more potent than erin as a surface anaesthetic agent.
Central actions of adenosine, a nucleotide of Ganoderma lucidum
Authors: Kasahara Yoshimasa , Hikino Hiroshi
Published: October 2006

In order to isolate an active constituent from the central inhibitory Ganoderma extract, an activity‐guided fractionation was performed to yield adenosine. Adenosine reduced spontaneous motor activity, elevated pain threshold, prolonged the death time induced by caffeine and relaxed skeletal muscle in mice.
Effect of bacosides A and B on avoidance responses in rats
Authors: Singh H. K. , Rastogi R. P. , Srimal R. C. , Dhawan B. N.
Published: October 2006

The nerve tonic activity of Bacopa monniera has been attributed to two saponins named Bacosides A and B. In the present investigation, Bacosides A and a mixture of the two saponins were used as aqueous suspensions. In the shock motivated brightness discrimination reaction a single oral dose of 10 mg/kg, 90 min prior to training, significantly reduced the time per trial, increased the number of positive responses and enhanced the relearning index. Similar effects were also observed in the relearning trial, but it was necessary to give a second dose 90 min prior to testing. In the active conditioned avoidance test 10 mg/kg p.o. given every alternate day significantly reduced the reaction time from the day 4 onward as well as the number of days of training. In the conditioned taste aversion response the bacosides produced a significant decrease in the lithium chloride intake. This effect was dose related in the range of 2.5–7.5 mg/kg p.o.

Bacosides appear to be promising compounds having facilitatory effect on mental retention capacity by improving responses with positive as well as negative reinforcement.
Reduced levels of glutathione in liver and tumour tissue of the mouse after administration of eupatoriopicrin
Authors: Woerdenbag H. J. , Malingré Th. M. , Lemstra W. , Konings A. W. T.
Published: October 2006

In this study the effect of the cytostatic acting sesquiterpene lactone eupatoriopicrin, isolated from Eupatorium cannabinum L., on gluthathione (GSH) levels in liver and tumour tissue of the mouse is described. C57Bl mice, bearing a solidly growing Lewis Lung carcinoma or a FIO 26 fibrosarcoma, with a volume between 500–1000 μL, were injected with eupatoriopicrin 20 or 40 mg/kg, intraperitoneally (i.p.) or intravenously (i.v.). At different time points, between 0–48 h after administration, the GSH content in liver and tumour tissue was determined. A dose dependent reduction of the GSH content was found. No difference in reduction was seen between i.p. and i.v. administration, but the route of administration appeared to be of great importance regarding acute toxicity: 40 mg/kg i.p. was lethal within 48 h, whereas mice receiving the same dose i.v. survived for over three months.
In vitro cytotoxicity of sesquiterpene lactones from Eupatorium cannabinum L. and semi‐synthetic derivatives from eupatoriopicrin
Authors: Woerdenbag H. J. , Hendriks H. , Malingré Th. M. , van Stralen R. , van den Berg K. J. , Konings A. W. T.
Published: October 2006

In this study 13 semi‐synthetic derivatives were prepared from the sesquiterpene lactone eupatoriopicrin, with the aim of obtaining compounds that are more active than eupatoriopicrin, and to give more insight into structure–activity relationships. The compounds were screened for cytotoxicity in vitro against the tumour cell lines EAT, P388, FIO 26, L5178Y(s) (murine) and HeLa (human). Cytotoxicity was compared with the germacranolides eupatoriopicrin, 5′‐dehydroxy eupatoriopicrin (‘compound 1’), hiyodorilactone E, eupatolide and eucannabinolide from Eupatorium cannabinum L. and with the eudesmanolides alantolactone and isoalantolactone from Inula helenium L. Acetalization of both hydroxyl groups in the ester side chain of eupatoriopicrin with acetone enhanced cytotoxicity 2–7‐fold. Introduction of bulky groups, such as alkyl groups with a longer carbon chain and (halogenated) acetophenone derivatives, via acetalization, reversed the enhancement. Oxidation at the germacrane ring structure of eupatoriopicrin acetonide, yielding an alcohol or an epoxy derivative, affected cytotoxicity adversely.
Positive inotropic action and conformation difference of lupin alkaloids in isolated cardiac muscle of guinea pig and bullfrog
Authors: Kimura Masayasu , Kimura Ikuko , Chui Li‐Hua , Okuda Shigenobu
Published: October 2006

The cardiac effects of the lupin alkaloids, matrine (Mat), allomatrine (Amat), oxymatrine (Omat), sophoridine (Sori) and sophoramine (Sora) were compared in guinea‐pig papillary muscle stimulated electrically and in isolated perfused bullfrog heart. Mat (0.4–2.4 mM), Amat (0.41–6.5 mM), Sori (0.68–6.3 mM) and Sora (0.61–6.5 mM) possessed positive inotropic effects, but not Omat (4.84 mM). The relative intrinsic activity was Amat>Mat>Sora>Sori. The effects of lupin alkaloids on isoproterenol (Isp)‐or Ca2+‐induced contraction were also tested in guinea‐pig papillary muscle. Mat, Amat, Sori and Sora, but not Omat, at a concentration (0.4 mM) inducing less or no inotropic effect, shifted the concentration‐response curves for Isp to the left and/or upward, and the maximal response of the concentration‐response curve for Ca2+ was only increased by Sora and Mat. The cardiotonic effects of lupin alkaloids were composed of: (1) potentiation of isoproterenol‐induced positive inotropic effects at low concentrations; and (2) a direct positive inotropic action at high concentrations. As the lupin alkaloids have similar chemical structures but different steric configurations, their patterns of cardiotonic actions were clearly different.
Inhibition of cell growth and macromolecule biosynthesis of human promyelocytic leukemic cells by acridone alkaloids
Authors: Chou Ting‐Chao , Tzeng Cherng‐Chyi , Wu Tian‐Shung , Watanabe Kyoichi A. , Su Tsann‐Long
Published: October 2006

Acridone alkaloids of plants indigenous to the Orient were isolated and purified, and their chemical structures were determined. A total of 50 acridones and their synthetic derivatives were subjected to rapid screening for inhibition of macromolecular synthesis using radiolabeled precursors of DNA, RNA and protein. These compounds were then studied to examine cell growth inhibition of human promyelocytic leukemic cells (HL‐60). Cytotoxicity was studied using the trypan blue exclusion method. Of 50 compounds evaluated for cell growth inhibition, 12 compounds showed IC50<10 μM; 12 compounds, 10‐20 μM; 8 compounds, 20‐100 μM; and 18 compounds, >100 μM.
Effect of aqueous extract of Adenia cissampeloides on blood pressure and serum analytes of hypertensive patients
Authors: Nyarko Alex A. , Addy Marian E.
Published: October 2006

Seven female hypertensive subjects, being treated with an aqueous extract of Adenia cissampeloides, (‘Adenia’), and seven weight‐, age‐ and sex‐matched hypertensive subjects about to begin treatment, were used to evaluate the therapeutic and possible toxic effects of this herbal preparation which is used at the Centre for Scientific Research into Plant Medicine (CSRPM), to control hypertension. Measurements of systolic and diastolic blood pressures were recorded, and serum levels of α‐hydroxybutyrate dehydrogenase (HBDH), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and creatine kinase (CK) were determined to give an indication of the effectiveness of ‘Adenia’ as an anti‐hypertensive agent. Serum levels of γ‐glutamyl transferase (GGT), alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin, proteins and cholesterol were used to indicate possible liver damage, and blood urea nitrogen (BUN), serum creatinine and creatinine clearance rate were determined for the assessment of possible nephrotoxicity. Systolic blood pressure was significantly lower in subjects on ‘Adenia’ compared to the control subjects not on ‘Adenia’. (p <0.01). HBDH and CK, were lower in the patients on ‘Adenia’, but the differences were not statistically significant. Levels of total and conjugated bilirubin were significantly lower in the subjects on ‘Adenia’, (P < 0.05). The plant preparation appears not to have hepatotoxic or nephrotoxic effects.
Plants as sources of antimalarial drugs. Part 7. Activity of some species of meliaceae plants and their constituent limonoids
Authors: Bray D. H. , Warhurst D. C. , Connolly J. D. , O'Neill M. J. , Phillipson J. D.
Published: October 2006

Crude extracts of three species of the Meliaceae family used traditionally as febrifuges (Azadirachta indica, Cedrela odorata, Guarea multiflora), together with 27 limonoids extracted from the meliaceous plants were evaluated for their in vitro antimalarial activity against chloroquine resistant K1 strain of Plasmodium falciparum. None of the extracts tested showed high antiplasmodial activity and only five compounds were found to be moderately active (IC50 values: 0.72–3.11 μ/mL). The most active limonoid, gedunin, of low in vitro cytotoxicity did not inhibit P. berghei in a 4 day test in mice (at the dose of 90 mg/kg/day, s.c. and i.p., no toxicity observed). Meliaceous plants may not exert their activity solely via direct action against malaria parasites, and the beneficial therapeutic effects claimed by patients might be due to the antiinnflammatory and immunomodulating activities recently described for these plants.
Transformation of aucubin to new pyridine monoterpene alkaloids, aucubinines A and B, by human intestinal bacteria
Authors: Hattori Masao , Kawata Yukio , Inoue Kazuyo , Shu Yue–Zhong , Che Qing–Ming , Namba Tsuneo , Kobashi Kyoichi
Published: October 2006

Aucubin was transformed to new nitrogen‐containing compounds named aucubinines A and B, along with an aglycone, aucubigenin by anaerobic incubation with defined strains of human intestinal bacteria and with faecal flora of humans. Among 24 bacterial strains examined, Klebsiella pneumoniae, Bifidobacterium breve, Bifidobacterium pseudolongum, Peptostreptococcus intermedius and Bacteroides fragilis showed potent ability of transforming aucubin to aucubinine A. Aucubinines A and B were prepared from aucubin by almond β‐glucosidase in the presence of NH.
Inhibitory actions of phospholipase A2 and saponins including ginsenoside Rb1 and glycyrrhizin on the formation of nicotinic acetylcholine receptor clusters on cultured mouse myotubes
Authors: Kobayashi Shinjiro , Nakagawa Masaya , Takahashi Kentaro , Kimura Ikuko , Kimura Masayasu
Published: October 2006

The effects of saponin(ICN), ginsenoside Rb1(G‐Rb1; 20‐S‐protopanaxadiol aglycon), ginsenoside Rg1(G‐Rg1; 20‐S‐protopanaxatriol aglycon), and glycyrrhizin (GLR) on acetylcholine receptor (AChR) cluster formation were investigated in developing mouse myotubes co‐cultured with spinal cord explants. Peak and total intensity of relative fluorescence in fluorescein isothiocyanate α‐bungarotoxin stain were measured as markers of AChR cluster formation and AChR appearance, respectively. Saponin (ICN) (1.0 μg/mL) inhibited both the cluster formation and the appearance of AChR on the plasma membranes of the myotubes. The effect of saponin (ICN) was closely related to extracellular Ca2+ ions, because its inhibition was abolished by treatment with 2 mM EGTA. G‐Rb1 also inhibited both markers at a higher concentration (122 μM), whereas G‐Rg1 had no effect. The effect of G‐Rb1 was not dependent on extracellular Ca2+ ions. GLR (122 μm) inhibited both markers, and its effect was decreased by 2 mM EGTA. At a lower concentration of 0.3 μ/mL, saponin (ICN) showed no direct effect; it did not affect inhibition of both markers by phospholipase A2(PLA2). In contrast, at a lower concentration (36 μM) without direct effect, both G‐Rb1 and GLR abolished the inhibition induced by PLA2. The modes of inhibitory actions of saponins on PLA2/Ca2+ interaction for the formation of AChR clusters were classified into three different interactions such as saponin (ICN) with the influx of external Ca2+, G‐Rb1 with PLA2, and GLR with PLA2/Ca2+/ calmodulin interaction.
Plant antiviral agents. VII. Antiviral and antibacterial proanthocyanidins from the bark of Pavetta owariensis
Authors: Baldé A. M. , van Hoof L. , Pieters L. A. , Berghe D. A. Vanden , Vlietinck A. J.
Published: October 2006

Extracts of the bark of Pavetta owariensis were found to exhibit in vitro antiviral and antibacterial activities. Bioassay‐gnided fractionation resulted in the isolation of new antimicrobially active dimeric, trimeric and tetrameric proanthocyanidins with doubly linked structures. The presence of (+)‐catechin and chlorogenic acid in the active fractions was also demonstrated.
Dietary Chlorella pyrenoidosa for patients with malignant glioma: Effects on immunocompetence, quality of life, and survival
Authors: Merchant Randall E. , Rice Charles D. , Young Harold F.
Published: October 2006

The scientific and anecdotal information available suggests that broken cell wall preparations and extracts of Chlorella pyrenoidosa in the diet provides important nutrients necessary to maintain good health, resist infection, and restore immune functions in immunocompromised patients. Our clinical study of Chlorella pyrenoidosa (provided by YSK International Corporation, Kyoto, Japan) was designed to test these properties in patients with a history of glioma. Patients with this type of primary brain tumor have a poor prognosis and either because of the tumor itself or due to the treatments applied to kill it, they have compromised immune functions leading to a greater than normal susceptibility to infection. Chlorella was added to the diet of 21 patients; 15 had a glioblastoma, four with low‐grade astrocytoma, one had an anaplastic astrocytoma, and one with a high‐grade oligodendroglioma. Each patient's general health was monitored by monthly physical and neurological examinations as long as they survived or for at least 2 years. Imaging studies of the brain and blood tests were performed at 3–4 months intervals. Complete blood counts, differentials, cytometric determinations of natural killer cells and T cell subsets, and in vitro lymphocyte activation assays to assess level of immunosuppression were performed on blood samples. Our results with patients taking Chlorella, although limited, suggest that the cellular components and functions of the immune system remain at near‐normal levels and are less adversely affected when patients are undergoing chemotherapy and/or taking immunosuppressive medications such as steroids. Over the 2 year course of our investigation, we have observed our patients to have had fewer respiratory infections and flu‐like illnesses. 7 of the 20 evaluable patients were alive and had yet to show any reappearance of their glioma after 2 years in the study. Although, our results suggest that our glioma patients may have benefited from adding Chlorella pyrenoidosa to their diet, more controlled clinical studies and animal experiments will be required to define its mechanism of action and limitations.
Effect of certain adaptogenic plant extracts on drug‐induced narcosis in female and male mice
Authors: Ahumada F. , Trincado M. A. , Arellano J. A. , Hancke J. , Wikman G.
Published: October 2006

The depressing effects of the extracts of Ocimun sanctum (O), Schizandra chinensis (S), Sedum rosea (R), Withania somnifera (W), Aralia elata (A), and Celastrus paniculatus (C) upon the mouse central nervous system (CNS) was evaluated. Recovery time of the righting reflex after the injection of a single dose of pentobarbital (50 mg/kg i.p.) was compared to the effect induced by that drug and the extracts. Decreasing or increasing the time for mouse recovery was evaluated in relation to dose and sex. The results demonstrate a significant (p ⩽ 0.05) increase of the narcosis time with all the extracts. The recovery of the righting reflex was sex and dose‐dependent. These plant extracts have a clear synergism with pentobarbital in depressing the mouse CNS response.
Anti‐diabetic effect of Nelumbo nucifera (Gaertn): Part I preliminary studies in rabbits
Authors: Huralikuppi J. C. , Christopher A. B. , Stephen P. M.
Published: October 2006

Nelumbo nucifera Gaertn, an Indian aquatic herb, has been studied for its potential utility in the treatment of Diabetes mellitus. The powdered sun‐dried flowers (test drug), as well as the aqueous and alcoholic extracts of these, produced significant hypoglycaemia in fasting normal albino rabbits. There was no significant difference in the activities of 1000 mg/kg of the test drug and equivalent amounts of the extracts; the effect was approximately 50% of that produced by 250 mg/kg of tolbutamide. Glucose tolerance studies with normal rabbits showed that oral doses of both extracts, equivalent to 1000 mg/kg of the test drug, produced significant depression of the peak rise in fasting blood sugar after glucose load; the effects of both extracts were comparable to that produced by 250 mg/kg of tolbutamide. A study of glucose tolerance curves shows that the duration of hyperglycaemia was also notably reduced compared with the controls. In normal rabbits, the extracts, in doses mentioned above, significantly depressed hyperglycaemia induced by injection of adrenaline hydrochloride 0.5 mg/kg s.c. Since the test drug and extracts were found to be effective in studies of the above parameters in normal animals, further chronic studies on normal and diabetic animals are planned.
Antiinflammatory activity of Ipomoea pes‐caprae (L.) R. Br
Authors: Pongprayoon U. , Bohlin L. , Soonthornsaratune P. , Wasuwat S.
Published: October 2006

The antiinflammatory activity of an extract from the leaves of Ipomoea pes‐caprae (L.) R. Br., used as a traditional remedy for different types of inflammation, was investigated using experimental models of acute inflammation. Topical application of the extract inhibited carrageenan‐induced paw oedema and ear oedema induced in rats by arachidonic acid or ethyl phenylpropiolate. In vitro prostaglandin formation was inhibited by the extract in a concentration‐dependent manner, with a potency equal to that of aspirin but considerably less than that of indomethacin. This study shows that Ipomoea pes‐caprae has a significant antiinflammatory activity, probably due to a reduction of prostaglandin and leukotriene formation. Thus, in addition to earlier results, this work further supports the use of Ipomoea pes‐caprae as an antiinflammatory agent in traditional medicine.