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At least 433 records · Page 24Linked to original sources
PubMed1987

Capillary supercritical fluid chromatography of pyrrolizidine alkaloids.

The application of capillary supercritical fluid chromatography (SFC) for the separation of pyrrolizidine alkaloids (PAs) is examined. Most of these compounds are powerful toxins. Because they are present in at least 3% of all flowering plants, they are responsible for serious losses of livestock and human disease. Capillary SFC, with its high separation efficiency, is shown to be an excellent method for the chromatographic analysis of complex PA mixtures. Complete separation of the PAs of the retronecine and otonecine family has been achieved by pressure-programmed capillary SFC. The operating conditions are mild enough to prevent thermal decomposition of the alkaloids during analysis.

Carbon Dioxide↗
PubMed1991

Red blood cells augment transport of reactive metabolites of monocrotaline from liver to lung in isolated and tandem liver and lung preparations.

Monocrotaline (MCT) is a pyrrolizidine alkaloid that causes pulmonary hypertension in rats by mechanisms which remain largely unknown. MCT is thought to be activated in the liver to a reactive intermediate that is transported to the lung where it causes endothelial injury. Our previous pharmacokinetic work demonstrated significant sequestration of radioactivity in red blood cells (RBCs) of rats treated with [14C]MCT. To determine whether this RBC sequestration might be important in the transport of reactive MCT metabolites, we compared the effect of inclusion of RBCs in the perfusion buffer on the extent of covalent binding of [14C]MCT to rat lungs in tandem liver-lung preparations. The potential effect of RBCs in stabilizing reactive intermediates was evaluated by preperfusion of isolated liver preparations with [14C]MCT with and without RBCs, separation and washing of the RBC fraction, and subsequent (90 min later) perfusion of washed RBCs or buffer alone in isolated perfused lungs. Covalent binding to lung tissues was determined by exhaustive methanol/chloroform extractions of unbound label from homogenized lung tissue followed by scintillation counting of residual 14C. Covalent binding was expressed as picomole MCT molecular weight equivalents/mg protein. Comparison of the relative capability of these isolated organ preparations for conversion of MCT to polar metabolites was done by extraction and HPLC analysis of perfusate at the end of the experiment. Isolated livers converted 65-85% of MCT to polar metabolites compared with less than 5% conversion in the isolated lungs. Inclusion of RBCs in the buffer of tandem lung liver preparations perfused with 400 microM [14C]MCT increased the covalent binding to the lung from 97 +/- 25 (buffer alone) to 182 +/- 36 (buffer + RBC) pmol/mg protein. At the end of these perfusions, RBCs contained 1552 +/- 429 pmol/mg hemoglobin of which 333 +/- 98 pmol/mg hemoglobin resisted exhaustive solvent extraction. After 90 min at room temperature, buffer with 400 microM [14C]MCT preperfused in isolated livers resulted in covalent binding to isolated perfused lung of 0.8 +/- 0.4 pmol/mg protein while washed RBCs isolated from buffer of similar liver preperfusions preparations resulted in 53 +/- 7 pmol/mg protein bound to lung. Control groups perfused with 400 microM [14C]MCT in buffer or buffer + RBCs through isolated lungs only resulted in covalent binding of 2 +/- 1 or 1 +/- 0.6 pmol/mg protein respectively. We conclude: (1) RBCs significantly augment the transport of lung reactive MCT metabolites from the liver to the lung.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1999

An intermediate-technology pattern matching model of veterinary diagnosis.

An intermediate-technology pattern matching model and decision support system for veterinary diagnosis is described. Six diseases of cattle occurring in the tropics are used to illustrate the model. The pattern matching model is composed of a series of transparent overlays and a template. Each transparent overlay represents a sign state and contains sign frequency information for the diseases on the template. By superimposing multiple transparent overlays upon the disease template, a ranked list of differential diagnoses can be obtained. Ranking is by summation of disease sign frequencies. Modifications to accommodate observational uncertainty are presented. Disease prevalences can be represented in the model.

Anaplasmosis↗
PubMed1978

Malignant neoplasms in rats fed lasiocarpine.

Lasiocarpine, a pyrrolizidine alkaloid, was fed at a dietary concentration of 50/10(6) for 55 weeks, to 20 male F-344 rats. Malignant tumours developed in 17/20 animals between 48 and 59 weeks. Forty-five percent (9/20) developed angiosarcomas of the liver and 35% (7/20) had hepatocellular carcinomas. Other tumours included malignant adnexas tumour of the skin (1 rat) and lympohoma (1 rat). Lung metastases were observed in 4 animals with angiosarcoma of the liver and one animal with hepatocellular carcinoma. From one animal, angiosarcoma was successfully transplanted through 4 generations.

Animals↗
PubMed1988

Magnesium aspartate hydrochloride attenuates monocrotaline-induced pulmonary artery hypertension in rats.

1. The effect of oral magnesium aspartate hydrochloride on monocrotaline (MCT)-induced pulmonary arterial hypertension was evaluated in rats. 2. A single subcutaneous injection of MCT, a pyrrolizidine alkaloid of plant origin, induces significant morphological changes in pulmonary vessels, pulmonary arterial hypertension and right ventricular hypertrophy in rats by 3 weeks. 3. Two groups of rats (Mg2+ control and Mg2+ + MCT) were started on oral Mg2+ (15.4 g/l magnesium aspartate hydrochloride dissolved in deionized water) 2 weeks before the MCT injection. The rest were given deionized water. At the start of the experiment, the control groups (deionized water and Mg2+) were given normal saline subcutaneously; the other groups (deionized water and Mg2+) were given MCT (60 mg/kg) subcutaneously. 4. Pulmonary artery pressure, right ventricular hypertrophy, lung pathology, organ weights and serum electrolytes were assessed 3 weeks after a single subcutaneous injection of MCT. Seventy-five per cent of the rats treated with MCT and oral Mg2+ (12 out of 16) showed significant reduction in pulmonary arterial hypertension, arterial pathology and right ventricular hypertrophy. 5. Our data indicate that Mg2+ attenuates experimentally induced pulmonary hypertension, possibly either by modulating the intracellular Ca2+ level and/or by directly affecting the pulmonary endothelial cell-smooth muscle cell complex involved in metabolism and maintenance of pulmonary vascular resistance.

Animals↗
PubMed2002

Intermedeol isolated from the leaves of Ligularia fischeri var. spiciformis induces the differentiation of human acute promyeocytic leukemia HL-60 Cells.

The present work was performed to investigate the effects of intermedeol on proliferation and differentiation of human leukemia-derived HL-60 cells as well as the underlying mechanisms for these effects. Intermedeol exhibited a potent antiproliferative activity against HL-60 cells. In addition, this compound was found to be a potent inducer for HL-60 cell differentiation as assessed by nitroblue tetrazolium reduction test, esterase activity assay, phagocytic activity assay, morphology change, and expression of CD14 and CD66b surface antigens. These results suggest that intermedeol induces differentiation of human leukemia cells to granulocytes and monocytes/macrophage lineage. Moreover, the expression level of c-myc was down-regulated during intermedeol-dependent HL-60 cell differentiation, whereas p21(CIP1) was up-regulated. Taken together, our results suggest that intermedeol may have potential as a therapeutic agent in human leukemia.

Antigens, CD↗
PubMed2003

Anti-platelet aggregation and chemical constituents from the rhizome of Gynura japonica.

A novel quinonoid terpenoid, (-)- alpha-tocospirone, a new chromanone, (-)-gynuraone, as well as three new steroids, (22 E,24 S)-7 alpha-hydroperoxystigmasta-5,22-dien-3 beta-ol, (22 E,24 S)-stigmasta-1,4,22-trien-3-one, and (24 R)-stigmasta-1,4-dien-3-one, together with 15 known components, were isolated from the rhizome of Formosan Gynura japonica. Structures of the new compounds were determined through spectral analyses and chemical evidence. Several of the isolated compounds, caryophyllene oxide, 6-acetyl-2,2-dimethylchroman-4-one, vanillin, 2,6-dimethoxy-1,4-benzoquinone, and benzoic acid exhibited significant anti-platelet aggregation activity in vitro.

Animals↗
PubMed2003

Contrasting dynamics in the same plant-herbivore interaction.

Long-term studies of two-species interactions under field conditions are unusual; most long-term field studies are of single species dynamics (1-6). Concurrent long-term studies on the dynamics of the same two interacting species in different locations are very rare. This result has led to the tacit assumption that different cases of the same two-species interaction would involve essentially quantitative differences (e.g., context-specific differences in the numeric values of demographic parameters like fecundity or death rates). Here, we show that for one of the best-known two-species systems (ragwort and cinnabar moth), this finding does not hold. The interaction between the plant and its herbivore is fundamentally different in coastal dunes in The Netherlands and in grasslands in Southeast England. In the first case, the dynamics are cyclic and the interaction involves both direct and delayed density dependence; in the second case, the insect has little impact on plant dynamics and there are no time lags in density dependence. The difference is caused by differences in the importance of seed-limitation in plant recruitment in the two locations.

Animals↗
PubMed1987

Modulation of monocrotaline-induced hepatic genotoxicity in rats.

Monocrotaline (MCT), a hepatotoxic/hepatocarcinogenic pyrrolizidine alkaloid (PA) induced DNA-DNA interstrand crosslinks in a dose-dependent manner through 30 mg/kg. Hepatic cytochrome P-450 has been shown to bioactivate MCT to pyrrole derivatives which are thought to be responsible for these genotoxic lesions. We have hypothesized these lesions to be related to the adverse hepatic actions of MCT and other PAs. Studies reported here investigated the effect of phenobarbital, a P-450 inducer, 2-dimethylaminoethyl-2,2-diphenylvalerate, a P-450 inhibitor and butylated hydroxyanisole, a dietary antioxidant, on hepatic DNA-DNA interstrand cross-links induced by a single dose of MCT (15 mg/kg i.p.) administered to male Sprague-Dawley rats. DNA damage was assessed by alkaline elution. The effects of these pretreatment regimens on MCT-induced DNA-DNA interstrand cross-linking was qualitatively similar to their reported effects on the hepatotoxicity of MCT. The effects of these pretreatments on hepatic cytochrome P-450 content, hepatic non-protein sulfhydryl levels and hepatic glutathione S-transferase activities were similarly investigated in attempts to explain the observed effects on DNA cross-link induction. These data provide further support for the association between DNA damage and the adverse hepatic effects of MCT.

Animals↗
PubMed1990

Effect of congestive heart failure on rate of atrial natriuretic factor release in response to stretch and isoprenaline.

STUDY OBJECTIVE: The aim was to investigate the pattern of release of atrial natriuretic factor induced by mechanical and adrenergic stimulation from atria of rats with or without congestive heart failure. DESIGN: Monocrotaline, a pyrrolizidine alkaloid, was given to rats to cause severe pulmonary hypertension, leading to a marked degree of right ventricular hypertrophy and failure. Measurements of noradrenaline and atrial natriuretic factor were performed in each cardiac chamber and in plasma. Right and left atria of control rats and rats with congestive heart failure were isolated and subjected to mechanical or adrenergic stimulation to study the in vitro release of atrial natriuretic factor. MATERIALS: Studies were performed on plasma, ventricles, and isolated right and left atria of 276 male Wistar rats, 80-100 g weight, with or without congestive heart failure. MEASUREMENTS AND MAIN RESULTS: In monocrotaline rats right and left ventricular concentrations of noradrenaline were significantly reduced. In the same rats concentrations of atrial natriuretic factor fell to 15.2% in the right atria and to 65.5% in the left atria. Whole heart content of atrial natriuretic factor was diminished, while plasma concentrations were increased sevenfold. Isolated hypertrophied right atria of failing hearts did not release atrial natriuretic factor in response to stretch or to isoprenaline (10(-9)M) and they were insensitive to the inotropic action of isoprenaline. On the other hand, non-hypertrophied left atria from the same animals released increased amounts of atrial natriuretic factor under basal conditions and after both stimuli, despite reduced tissue stores of the peptide. CONCLUSIONS: Heart failure may deplete cardiac stores of noradrenaline and atrial natriuretic factor, especially in hypertrophied chambers, and can result in a decrease in the release of atrial natriuretic factor from atrial tissue in response to mechanical and adrenergic stimulation.

Animals↗
PubMed1978

Effects of monocrotaline pretreatment of rats on removal of 5-hydroxytryptamine and noradrenaline by perfused lung.

1 The alkaloid, monocrotaline, causes significant pulmonary damage in many species, including the rat. We, therefore, determined whether the inactivation of biogenic amines by perfused lungs of rats was modified by prior treatment of the animals with monocrotaline.2 Young rats (45 to 50 g) treated for 21 days with monocrotaline (22 mug/ml) in their drinking water developed right ventricular hypertrophy. Treated animals gained weight more slowly and consumed less food and water than control rats that drank tap water. Lungs from monocrotaline-treated animals were heavier and had a higher protein content than control lungs.3 Isolated lungs from treated animals removed and metabolized 50% less perfused 5-hydroxytryptamine than did controls.4 The diminished 5-hydroxytryptamine metabolism was probably due to impaired delivery of substrate to intrapulmonary monoamine oxidase (MAO) since MAO activity in 600 g supernatant fractions of homogenates of lungs from monocrotaline-treated rats was not different from control values.5 Pulmonary removal of perfused noradrenaline was decreased about 60% by the 21-day treatment, suggesting that the effects of monocrotaline were somewhat nonspecific.6 These effects were not caused by monocrotaline directly, since perfusion of lungs from untreated animals with this drug did not alter removal of co-perfused 5-hydroxytryptamine.7 Reduced pulmonary removal of circulating biogenic amines following pretreatment with monocrotaline may reflect damage to capillary endothelium, which could also affect other metabolic functions of lung.

Animals↗