bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lung tumor induction in A/J mice and clastogenic effects in CD‐1 mice of the sequence‐selective DNA alkylating agents (+)‐cc‐1065 and (−)‐cc‐1065
Authors: Linseman Daniel A. , Branstetter Daniel G. , Yu Roger L. , Aaron C. S. 
Published: October 2006

AbstractThe in vivo genotoxic effects of the antitumor antibiotic, (−)‐CC‐1065, and its unnatural enantiomer, (−)‐CC‐1065, were investigated in two mouse models. These two compounds alkylate AT‐rich regions of double stranded DNA with distinct sequence selectivities.(+)‐CC‐1065 dose‐dependently increased the chromosomal aberration frequency in bone marrow cells of CD‐1 mice from 1.2 ± 0.8% in vehicle control animals to 5.0 ± 1.2%, 11.4 ± 3.9%, and 20.6 ± 2.3% 24 hours following single intravenous doses of 2, 4, and 8 μg/kg, respectively. (−)CC‐1065 was significantly less potent with a maximal response at 8 μg/kg approximately one‐third of that observed for (+)‐CC‐1065.(+)‐CC‐1065 induced a significant (P ± 0.05), three‐fold increase in the number of lung tumors/mouse in strain A/J mice from 0.27 ± 0.15 for vehicle control animals to 0.83 ± 0.15 24 weeks following a single intravenous dose of 8 μs/kg. This effect was paralleled by corresponding threefold increases in the percentage of mice with tumors and the percentage of mice with multiple tumors, compared to vehicle controls. (−)‐CC‐1065 at 8 μg/kg induced 0.67 ± 0.15 tumors/mouse and resulted in slightly smaller increases in the tumor incidence and multiple tumor incidence, compared to (+)‐CC‐1065.The above results demonstrate that single intravenous doses of (+)‐CC‐1065 and (−)‐CC‐1065 which cause chromosomal damage in CD‐1 mice also induce an increased incidence of lung tumors in A/J mice. (+)‐CC‐1065 may have a slightly greater genotoxic potential in vivo than its unnatural enantiomer. This may be attributable to differences in the DNA binding sequence selectivities of the two compounds. Furthermore, when compared on a μ‐moles/kg basis, (+)‐CC‐1065 is > 7,000 × more potent than N‐ethyl‐N‐nitrosourea at inducing a similar tumorigenic response in the A/J mouse lung tumor bioassay. © 1995 Wiley‐Liss, Inc.
Effect of T‐2 toxin and verrucarin A in combination on Kluyveromyces marxianus
Authors: Jones Tania J. , Koshinsky Heather A. , Khachatourians George G. 
Published: October 2006

AbstractThe growth inhibitory effects of combinations of T‐2 toxin and verrucarin A on the yeast Kluyveromyces marxianus was studied. A combination index value was derived to indicate the type of interaction that existed between the binary mixture of these two toxins at various ratios and the target yeast cells. The type of interaction was dependent on the ratio of the toxins used to attain a particular level of growth inhibition. Further, the least change in the type and intensity of interaction or the maximally quiescent ratio (MQR) was found to be unique to the growth medium. In a rich medium, the MQR was 1.0 μg/ml T‐2 toxin:0.75 μg/ml verrucarin A, where the two toxins had a very stable synergistic interaction over a 2 or 3 log value concentration range. Decreasing the nutrients changed the MQR to 1.0 μg/ml T‐2 toxin: 0.38 μg/ml verrucarin A. Halving the concentration of the cells in the assay changed the MQR to 1.0 μg/ml T‐2 toxin.6.0 μg/ml verrucarin A. We have previously shown that the hierarchy of trichothecene toxicity in yeast bioassay is verrucarin A > roridin A > T‐2 toxin > diacetoxyscirpenol > HT‐2 toxin. The MQR of these toxins in combination with T‐2 toxin follows the same order. This study shows an exception to the above order in that verrucarin A and roridin A exchange places. © 1995 Wiley‐Liss, Inc.
Fumonisins: Their implications for human and animal health
Authors: Marasas Walter F. O. 
Published: October 2006

AbstractFusarium moniliforme is one of the predominant fungi associated with com intended for human and animal consumption world‐wide. Fumonisins, food‐bome carcinogens that occur naturally in com, were first isolated and chemically characterized in South Africa in 1988. The major metabolite, fumonisin B1 (FB1), was subsequently shown to cause leukoencephalomalacia (LEM) in horses, pulmonary edema syndrome (PES) in pigs, and liver cancer in rats. FB1, is also a cancer promoter and initiator in rat liver; hepatotoxic to horses, pigs, rats, and vervet monkeys; cytotoxic to mammalian cell cultures; and phytotoxic to several plants. Fumonisins in home‐grown com have been associated with an elevated risk for human esophageal cancer in Transkei and China. There is a close structural similarity between fumonisin and sphingosine, and fumonisins are the first known naturally occurring inhibitors of sphingolipid biosynthesis. The natural occurrence of FB1 together with FB2 and FB3, has been reported in commercial com and/or combased feeds and foods from Argentina, Australia, Brazil, Botswana, Bulgaria, Canada, China, Egypt, France, Italy, Japan, Kenya, Hungary, Nepal, Peru, South Africa, Switzerland, United States, and Zimbabwe. It is imperative that safe levels of fumonisins in human foods and animal feeds should be determined and realistic tolerance levels established as soon as possible. © 1995 Wiley‐Liss, Inc.
Some reflections on establishing a community legislation on mycotoxins
Authors: Verardi Giuseppe , Rosner Heino 
Published: October 2006

AbstractA Community legislation on mycotoxins is essential to protect public health and to avoid trade barriers and competition distortions. Maximum permitted levels in food are to be fixed. Some orientations for this purpose are indicated.The verification of the compliance with maximum permitted levels shall need suitable analytical methods. Up to now, such methods were fixed by directives. This approach, however, had some disadvantages. A more flexible approach is to be planned.Among the mycotoxins to be taken into consideration, priority should be granted to the aflatoxins and to ochratoxin A. Fumonisins also deserve interest. Other mycotoxins will be taken into consideration as the need arises and scientific data are available.Some basic remarks on the rationale for establishing maximum permitted levels in food are made. © 1995 Wiley‐Liss, Inc.
Drugs that show protective effects from ricin toxicity in in vitro protein synthesis assays
Authors: Thompson William L. , Scovill John P. , Pace Judith G. 
Published: October 2006

AbstractWe used an in‐vitro, inhibition of protein synthesis assay (PSI) to test a wide variety of drugs for possible therapeutic use against ricin, a toxic glycoprotein that causes death in animals by inhibiting protein synthesis. Selection of test drugs was based on possible interference with ricin activity at different stages of the toxic process. Most of the drugs tested had no effect on ricin‐induced PSI, were toxic when tested alone, or enhanced the toxicity of ricin. The only ones showing protection were galactose, lactose, and several derivatives of these sugars, Brefeldin A (BFA), 3′‐azido‐3′‐deoxythymidine (AZT), and a purine derivative (BM33203). The sugar derivatives provided 50% protection against a PSI ED99 of ricin (0.1 μg/ml). Concentrations of BFA greater than 0.5 μM caused about 50% PSI by itself, but blocked any further inhibitory effects of ricin. AZT, at optimum concentrations, reached a maximum protection level of about 40% in the presence of an ED99 dose of ricin, while the nucleoside derivative, BM33203, at concentrations above 0.1 mM, showed minimal protection (up to 30%) from ricin toxicity. The combination of BM33203 and AZT appeared to have an additive effect, showing up to 80% protection from an ED dose of ricin. Drugs showing protection in the PSI cell assay showed no protection from ricin in a cell‐free translation assay used to determine if they would block ricin at the protein synthesis site. © 1995 Wiley‐Liss, Inc.
Postpartum intracerebral hemorrhage in a patient receiving bromocriptine
Authors: Iffy Leslie 
Published: October 2006

AbstractA case of intracerebral hemorrhage is described which occurred on the 4th day of the puerperium in a patient who had mild pregnancy induced hypertension. The mother received bromocriptine for milk suppression following childbirth; a drug with demonstrated potential for exacerbating hypertension. The rarity of such accidents postpartum, projected against the increasing number of reports documenting vasospastic effect of bromocriptine in the puerperium, increases the suspicion concerning a cause‐effect relationship.
Automated databases and the need for fieldwork in pharmacoepidemiology
Authors: Hemmelgarn Brenda , Blais Lucie , Collet Jean‐Paul , Ernst Pierre , Suissa Samy 
Published: October 2006

AbstractThe Saskatchewan Asthma Epidemiologic Project (SAEP) is used as an example to describe the fieldwork necessary to supplement computerized data sources. Steps were implemented beyond the computerized sources of information to identify case events, validate outcome diagnoses, and obtain clinical information on potential confounding variables. Validation of the cause of death as actually being a consequence of asthma was particularly beneficial and prevented the misclassification of 11 of the 165 deaths identified from a geographically defined cohort of asthmatic patients in the province of Saskatchewan. Hospital medical records and physician questionnaires were used in the SAEP as an external source of information in an attempt to measure and control asthma severity, a potential confounding variable. The availability of a variety of variables which contributed to the measure of asthma severity from hospital medical records and physician questionnaires was highly variable, ranging from 4 per cent to 86 per cent. A considerable amount of time and expense was associated with obtaining additional information beyond the automated databases.
The effect of the introduction of safety packaging for carbamazepine on toxicity in overdose in adults
Authors: Buckley N. A. , Newby D. A. , Dawson A. H. , Whyte I. M. 
Published: October 2006

AbstractBackground — Safety packaging has been shown to be effective in preventing childhood poisoning; however similar data for adults is lacking. In February 1993 the Australian packaging for carbamazepine was changed from bottles of tablets to blister packs.Objective — To assess whether there has been a change in the amount of carbamazepine taken per overdose or the severity of poisoning coinciding with this change.Design — Comparison of cohorts of patients presenting before and after repackaging.Setting — Newcastle, Australia.Subjects — Sixty‐seven patients who ingested carbamazepine and presented to a general hospital which serves a well‐defined geographic area.Main outcome measures — Number of tablets and total dose ingested, peak carbamazepine level, degree of sedation, need for intubation and the time in hospital and ventilated.Results — Significantly fewer tablets and a lesser amount was ingested by patients presenting after the repackaging. Though clinical measures were improved slightly after repackaging the differences did not reach statistical significance.Conclusions — Repackaging resulted in less carbamazepine reported to have been ingested in overdose. Clinical measures did not reflect the extent of this change. This may be due to effects of treatment or coingested drugs obscuring any difference or the reported differences may be due to a reporting bias associated with packaging. Repackaging is a promising means of reducing the severity of deliberate self poisoning but further study, including out of hospital mortality data, is required.
The interaction of natural products with cellular signalling mechanisms
Authors: Drummond Alan H. , Hughes Phil. J. 
Published: October 2006

AbstractNaturally occurring substances were of inestimable value to the founding fathers of modern pharmacology in their early studies into the nature and properties of neurotransmitter receptors. Even today, chemical substances derived from the animal and plant kingdom are of crucial importance to biochemical pharmacologists studying the mechanisms by which hormonal signals are communicated from the cell surface to the intracellular compartment. Signal transduction is a complex procedure which involves the linkage of a receptor, via a coupling protein (usually a guanine nucleotide binding protein or G‐protein), to a system which produces second messengers (adenylate cyclase, phosphoinositidase C or an ion channel) or directly to an ion channel. Not only has nature provided a variety of agents that can mimic or antagonize the actions of hormones at the cell surface, but it has also provided a wealth of substances that can modify the signal transduction process at a post receptor level. In this article, we discuss the sources and the mechanisms of action of a selection of the most widely used of these latter agents and show how they have helped the modern biochemical pharmacologist to gain an insight into the fundamental mechanisms involved in signal transduction.
Plants as a source of antimalarial drugs 5. Activities of Ailanthus altissima stem constituents and of some related quassinoids
Authors: Bray D. H. , Boardman P. , O'Neill M. J. , Chan K. L. , Phillipson J. D. , Warhurst D. C. , Suffness M. 
Published: October 2006

AbstractExtracts from Ailanthus altissima (Mill.) Swingle Simaroubaceae have been tested for activity against Plasmodium falciparum in vitro and against P. berghei infections in mice. The activity of the chloroformic extract in vitro (IC50 5 μg ml‐1) and in vivo (ED50 82.94 mg kg −1 d −1 after oral administration) is due principally to the presence of the quassinoid ailanthone (IC50 in vitro 0.015μg ml−1 ED50 in vivo 0.76 mg kg−1 d−1). The constituent alkaloids canthin‐6‐one and 1‐methoxycanthin‐6‐one are inactive in vitro. The in vitro and in vivo antimalarial activities of five related quassinoids, viz., ailanthinone, chaparrin, glaucarubol, glaucarubin, glaucarubinone are also reported.
Cytostatic activity of eupatoriopicrin in fibrosarcoma bearing mice
Authors: Woerdenbag H. J. , Malingré Th. M. , Lemstra W. , Konings A. W. T. 
Published: October 2006

AbstractIn this study the possible cytostatic effects of eupatoriopicrin, a sesquiterpene lactone isolated from Eupatorium cannabinum L., against the fibrosarcoma FIO 26 have been investigated. This solidly growing tumour was transplanted subcutaneously in C57Bl mice. Eupatoriopicrin was administered intraperitoneally (as single as well as repeated doses) as a solution in 20% v/v ethanol. Different doses and dosage schedules were used and compared with control conditions. A dose dependent growth delay of the tumour was found. The treating volume of the tumour was about 500 μl. Two clinically applied chemotherapeutics, doxorubicin and cyclophosphamide, were used as reference compounds.
Pharmacological evidence for an interaction between constituents (blend effect) of the Japanese‐Sino medicine “Keishi‐ka‐zyutubu‐tō” in neuromuscular blockade in diabetic mice
Authors: Kimura Masayasu , Kimura Ikuko , Muroi Masashi , Yoshizaki Masao , Hikino Hiroshi 
Published: October 2006

AbstractThe pharmacological interaction between constituents of Keishi‐ka‐zyutubu‐tō (composed of 7 crude drugs, namely peony, liquorice, jujube, cassia, ginger, Atractylodes lancea, and aconite), a medicine of Japanese‐Sino origin, was investigated in in situ sciatic nerve‐gastrocnemius muscle preparations using genetically dlabetic KK‐CAy mice. When administered intra‐arterially, the drug caused a degree of inhibition of the diabetic neuromuscular junction 280 times greater than normal. The two constituents, peony‐liquorice, were only 2.6 times more potent in diabetic muscles. When further combined with peony‐liquorice, the potency ratio was increased 4.9 times for cassia, 5.9 times for ginger and 8.7 times for Atractylodes lancea. In combination with the representative compounds contained in the above crude drugs except for jujube, the potency ratio of paeoniflorin (PF) and glycyrrhizin (GLR) was increased 6.6 times for cinnamaldehyde, 6.1 times for [8]‐gingerol and 14 times for β‐eudesmol in diabetic muscles. Aconite potentiated the blocking effects of peony‐liquorice to the same extent in diabetic muscles as in normal muscles. This tendency was also confirmed when mesaconitine was combined with PF‐GLR. The single effect of β‐eudesmol or [8]‐gingerol was 5.2 times or 3.7 times more potent, respectively, on diabetic muscles than on normal muscles. Cinnamaldehyde or mesaconitine demonstrated the same degree of sensitivity in both diabetic and normal muscles. These results indicated that the preferentially more potent neuromuscular blocking effects of Keishi‐ka‐zyutubu‐tō in diabetic muscles were mainly attributable to β‐eudesmol, a major component of Atractylodes lancea.
Influence of side chains on phorbol ester binding to protein kinase C
Authors: Yeh Emily , Sharkey Nancy A. , Blumberg Peter M. 
Published: October 2006

AbstractThe phorbol esters, natural products derived from plants of the family Euphorbiaceae, are potent tumor promoters and modulators of biological response. Their major site of action is protein kinase C. Three classes of derivatives were examined to better assess the influence of the ester side chains on phorbol ester binding affinity for protein kinase C. A series of phorbol diesters substituted at the 13‐OH with biotin separated from the phorbol nucleus by linker arms of variable length were prepared. Although all showed good potency by themselves (half‐maximally effective doses of 12–67 nM), addition of avidin greatly inhibited activity, suggesting significant steric constraints on the side chains for retention of activity. At the other extreme, very high concentrations of the unsubstituted parent alcohol phorbol were examined to determine whether phorbol was actually inactive or whether it might simply possess weak binding activity. Inhibition was in fact observed with an apparent Ki of approximately 10 mM. The inhibition was time dependent and not stereospecific, however, suggesting that the inhibition was not due to competitive binding. The third class of compounds examined were phorbol 12‐ and 13‐monoesters. Although approximately 20‐fold less potent than the 13‐monoesters, the 12‐monoesters showed substantial binding activity, in contrast to their reported lack of activity in vivo.
A pharmacological study of Glaucium flavum Crantz II: Central nervous system
Authors: Cabo J. , Cabo M. P. , Jimenez J. , Zarzuelo A. 
Published: October 2006

AbstractA series of neuropharmacological studies were carried out on several preparations of the root, leaves, stem and pericarps of the fruit of Glaucium flavum Crantz in experimental animals. In general administration these preparations produced a lowering of spontaneous activity and body temperature, potentiation of barbiturate‐induced sleep and analgesia. These results indicate that Glaucium flavum has a clearly depressive action on the CNS.
The effects of phorbol esters with different biological activities on protein kinase C
Authors: Ellis Christine A. , Brooks Susan F. , Brooks Gavin , Tudor Evans A. , Morrice Nicholas , Evans Fred. J. , Aitken Alastair 
Published: October 2006

AbstractThe sapintoxins are a series of naturally occurring fluorescent phorbol esters with a range of selective biological activities (e.g. pro‐inflammatory but non‐tumour promoting). Their ability to activate protein kinase C (PKC) in vitro has been studied. Both tumour promoting and non‐promoting phorbol derivatives activate the enzyme in vitro at low concentrations. 12‐deoxyphorbol‐13‐phenylacetate‐20 acetate (DOPPA) acts as a partial agonist in the activation of protein kinase C. Structurally distinct phorbol esters may therefore preferentially activate different forms of protein kinase C. α‐sapinine, a biologically inactive compound, binds to protein kinase C without stimulating the enzyme and prevents subsequent activation by phorbol esters such as 12‐O‐tetradecanoyl phorbol‐13‐acetate (TPA).
A sensitive micro‐method for the quantitation of total alkaloids seasonal effect on alkaloid accumulation in leaves of Datura metel grown in Ibadan
Authors: Abo K. A. , Ikhile B. U. 
Published: October 2006

AbstractThe analytical method described is a rapid means of assay for total alkaloids, using a back titration with acid employing a potentiometric determination of end‐point. Samples required (approx. 1.5 g) are much less than those for conventional percolation processes. Using the procedure, the total alkaloid content of Datura metel has been shown to peak in the hot dry season, only minimal levels of bases being detected in the rainy season in Ibadan.
Natural antagonists of platelet‐activating factor
Authors: Hosford David , Mencia‐Huerta Jean‐Michel , Page Clive , Braquet Pierre 
Published: October 2006

AbstractSeveral groups of antagonists of platelet‐activating factor (PAF) are reviewed. The characteristics of PAF binding sites on mammalian cell membranes are described together with the activities of non‐specific and synthetic PAF‐antagonists. The specificity of the ginkgolides to bind to PAF‐receptors is discussed and the effects of these natural products in a range of biological systems is emphasized. Other groups of natural PAF‐antagonists described are the lignans and gliotoxin related compounds. The structural chemistry, structure‐activity relationships and pharmacological properties of these drugs are compared to the ginkgolides.
Effect of (−)‐cathinone, an active principle of Catha edulis forssk. (Khat) on plasma amino acid levels and other biochemical parameters in male wistar rats
Authors: Al‐Meshal I. A. 
Published: October 2006

AbstractLeaves of the psycho‐active plant Catha edulis (khat) have been used in traditional medicine for the treatment of depression, fatigue, obesity and gastric ulcers. (−)‐Cathinone is considered as the major chemical ingredient in khat leaves responsible for the CNS effects of the plant. In recent years many reports have been published on neuropharmacological aspects of this compound. Little is known about its metabolic and biochemical changes in vivo, following ingestion. In the present study two groups of male albino rats were dosed with 30 and 100 mg/kg, body weight of cathinone, respectively. The animals were sacrificed after one hour of administration. Blood and heart muscle samples were collected for the analysis of amino acids, acid phosphatase, alkaline phosphatase, cholesterol, glucose, SGDT, SGPT, triglycerides, urea, uric acid and cardiac glycogen. (−)‐Cathinone in lower dose (30 mg/kg) significantly increased 12 and decreased 1 out of 22 amino acids studies, whereas in higher dose (100 mg/kg) it significantly decreased 20, and increased 1 amino acid level. There was a decrease in cardiac glycogen and serum triglycerides with both the dose of cathinone used. Other biochemical parameters remained unchanged.
Effect of padma 28 on experimental hyperlipidaemia and atherosclerosis induced by high‐fat diet in rabbits
Authors: Wójcicki J. , Samochowiec L. , Ceglecka M. , Juzyszyn Z. , Tustanowski S. , Kadłubowska D. , Juźawiak S. 
Published: October 2006

AbstractNew Zealand rabbits were divided into three equal groups: (1) controls, (2) animals receiving high‐fat diet (HFD) containing cholesterol and coconut oil, and (3) HFD + Padma 28. A pronounced reduction in lipid metabolism disturbancs and in severity of plaque formation occurred after Padma 28 had been administered. Lipid content in serum, lever homogenate and liver microsomes was depressed. An increase in the microsomal phosphatidylcholine content was observed. The cytochrome P‐450 content in liver microsomes was significantly elevated, and the concentration of malondialdehyde in the blood serum of rabbits was decreased whilst insulin levels were normalized and testosterone content was increased. Atherosclerotic plaque intensity at 12 weeks measured planimetrically averaged 67.3% in HFD‐fed animals but only 15.5% in Padma 28‐treated rabbits. These findings suggest that Padma 28, in addition to lowering serum lipid level in rabbits on an experimental diet also affect metabolic processes in the liver and may modify lipid deposition in major arteries.