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Swainsonine toxicosis mimics lectin histochemistry of mannosidosis.

Cells affected by locoweed (Astragalus lentiginosus) and Swainsona galegifolia toxicosis or mannosidosis exhibit similarities in their catabolism of N-linked glycoproteins and accumulation of cytoplasmic vacuoles. We used nine different biotinylated lectins as histochemical markers for specific sugars and avidin-biotin-peroxidase complex as a visualant to study the cells affected with these conditions. Since locoweed and Swainsona spp block mannosidase activity, we expected a similar lectin staining pattern in cells under these conditions as that seen in mannosidosis. Concanavalia ensiformis agglutinin, wheat germ agglutinin and succinyl wheat germ agglutinin stained the undegraded glycoproteins and oligosaccharides stored in the lysosomes of affected cells in all three conditions. Bandeirea simplicifolia-I, Dolichos biflorus agglutinin, peanut agglutinin, Ricinus communis agglutinin-I, soybean agglutinin and Ulex europaeus agglutinin-I did not stain any of these cells. These results indicate that in all three conditions there is an accumulation of undegraded oligosaccharides that contain alpha-mannosyl and beta-N-acetyl glucosamine residues which are revealed by lectin staining in the vacuoles of all affected cells.

Alkaloids↗

A lysosomal storage disease induced by Ipomoea carnea in goats in Mozambique.

A novel plant-induced lysosomal storage disease was observed in goats from a village in Mozambique. Affected animals were ataxic, with head tremors and nystagmus. Because of a lack of suitable feed, the animals consumed an exotic hedge plant growing in the village that was identified as Ipomoea carnea (shrubby morning glory, Convolvulaceae). The toxicosis was reproduced by feeding I. carnea plant material to goats. In acute cases, histologic changes in the brain and spinal cord comprised widespread cytoplasmic vacuolation of neurons and glial cells in association with axonal spheroid formation. Ultrastructurally, cytoplasmic storage vacuoles in neurons were membrane bound and consistent with lysosomes. Cytoplasmic vacuolation was also found in neurons in the submucosal and mesenteric plexuses in the small intestine, in renal tubular epithelial cells, and in macrophage-phagocytic cells in the spleen and lymph nodes in acute cases. Residual alterations in the brain in chronic cases revealed predominantly cerebellar lesions characterized by loss of Purkinje neurons and gliosis of the Purkinje cell layer. Analysis of I. carnea plant material by gas chromatography-mass spectrometry established the presence of the mannosidase inhibitor swainsonine and 2 glycosidase inhibitors, calystegine B2 and calystegine C1, consistent with a plant-induced alpha-mannosidosis in the goats. The described storage disorder is analogous to the lysosomal storage diseases induced by ingestion of locoweeds (Astragalus and Oxytropis) and poison peas (Swainsona).

Animals↗

Dose response of sheep poisoned with locoweed (Oxytropis sericea).

Locoweed poisoning occurs when livestock consume swainsonine-containing Astragalus and Oxytropis species over several weeks. Although the clinical and histologic changes of poisoning have been described, the dose or duration of swainsonine ingestion that results in significant or irreversible damage is not known. The purpose of this research was to document the swainsonine doses that produce clinical intoxication and histologic lesions. Twenty-one mixed-breed wethers were dosed by gavage with ground Oxytropis sericea to obtain swainsonine doses of 0.0, 0.05, 0.1, 0.2, 0.4, 0.8, and 1.0 mg/kg/day for 30 days. Sheep receiving > or = 0.2 mg/kg gained less weight than controls. After 16 days, animals receiving > or = 0.4 mg/kg were depressed, reluctant to move, and did not eat their feed rations. All treatment groups had serum biochemical changes, including depressed alpha-mannosidase, increased aspartate aminotransferase and alkaline phosphatase, as well as sporadic changes in lactate dehydrogenase, sodium, chloride, magnesium, albumin, and osmolarity. Typical locoweed-induced cellular vacuolation was seen in the following tissues and swainsonine doses: exocrine pancreas at > or = 0.05 mg/kg; proximal convoluted renal and thyroid follicular epithelium at > or = 0.1 mg/kg; Purkinje's cells, Kupffer's cells, splenic and lymph node macrophages, and transitional epithelium of the urinary bladder at > or = 0.2 mg/kg; neurons of the basal ganglia, mesencephalon, and metencephalon at > or = 0.4 mg/kg; and cerebellar neurons and glia at > or = 0.8 mg/kg. Histologic lesions were generally found when tissue swainsonine concentrations were approximately 150 ng/g. Both the clinical and histologic lesions, especially cerebellar lesions are suggestive of neurologic dysfunction even at low daily swainsonine doses of 0.2 mg/kg, suggesting that prolonged locoweed exposure, even at low doses, results in significant production losses as well as histologic and functional damage.

Animals↗

Total astragaloplasty.

Four cases are presented of astragular arthrosis treated with substitution of the entire astragalus with a prosthesis identical in form to that bone. The four cases were due to severe fracture, avascular necrosis, and degenerative joint disease. One patient died of a heart attack 6 months after the operation, the other three cases, one of them with a 6-year follow-up, present a good result. The presentation is made to illustrate the clinical progress of treatment of talar arthroses.

Acrylic Resins↗

Influence of traditional Chinese anti-inflammatory medicinal plants on leukocyte and platelet functions.

The enzymes 5-lipoxygenase and elastase are therapeutic targets in dermatological disorders such as psoriasis. Fifteen extracts from traditional Chinese medicinal plants used to treat topical inflammations were screened for their inhibitory effect on lipoxygenase, cyclooxygenase and elastase activity in intact leukocytes and platelets. Astragalus membranaceus, Forsythia suspensa and Poria cocos inhibited 5-lipoxygenase, with IC50 values of 141, 80 and 141 microg mL(-1), respectively. The latter two species, along with Angelica dahurica and Angelica pubescens, also inhibited elastase (IC50 values of 80, 123, 68 and 93 microg mL(-1), respectively), while A. pubescens, Atractylodes macrocephala, Lentinus edodes, Rehmannia glutinosa and Paeonia lactiflora selectively inhibited 12-(S)-HHTrE production, a valid marker of cyclooxygenase activity. The inhibition of phospholipase A(2) activity by P. cocos is discussed. Dehydrotumulosic and pachymic acids, which have been isolated from P. cocos, were shown to inhibit leukotriene B(4) release. The results indicate that both P. cocos and F. suspensa are potentially valuable species in the management of skin pathologies involving chronic inflammation.

Animals↗

Study of structure--hepatoprotective relationships of oleanene-type triterpenoidal glucuronides obtained from several fabaceous plants on rat primary hepatocyte cultures.

The protective effects of nine oleanene-type triterpenoidal glucuronides obtained from several fabaceous plants (Lupinus polyphyllus x arboreus Hybrid, Astragalus complanatus, Wistaria brachybotrys) on in vitro immunological liver injury in primary cultured rat hepatocytes were studied. Although all tested saponins showed hepatoprotective action, the levels of activity of the individual saponins differed. Structure-activity relationships for the sapogenol moiety suggested that the presence of the carbonyl group at C-22 would show a similar hepatoprotective effect to that of the hydroxyl group at C-22 while the presence of the hydroxyl group at C-30 would reduce the hepatoprotective action. This structure-activity relationship substantiated other recently obtained data. Furthermore, the beta-orientation of the hydroxyl group at C-21 is more effective than the alpha-configuration in regard to the hepatoprotection. Furthermore, structure-activity relationships for the sugar moiety substantiated previously obtained data that the hydroxyl group at C-5" enhances the hepatoprotective action.

Animals↗

Anti-hyperglycemic effect of fangchinoline isolated from Stephania tetrandra Radix in streptozotocin-diabetic mice.

Kampo medicine, Stephania tetrandra Radix (Stephania) in Boi-ogi-to increases the blood insulin level and falls the blood glucose level in streptozotocin (STZ)-diabetic ddY mice. These actions of Stephania are potentiated by Astragalus membranaceus Bunge Radix (Astragali) in Boi-ogi-to (Liu et al., J. Traditional Med., 17, 253-260, 2000). In the present study, actions of bis-benzylisoquinoline alkaloids isolated from Stephania were investigated in the hyperglycemia of STZ-diabetic mice. A main bis-benzylisoquinoline alkaloid, fangchinoline (0.3-3 mg/kg) significantly fell the blood glucose level of the diabetic mice in a dose-dependent manner. The effect of fangchinoline was 3.9-fold greater than that of water extract of Stephania. However, another main compound, tetrandrine (1-100 mg/kg) did not have any effect. The water extract of Astragali did not affect singly but potentiated the anti-hyperglycemic action of fangchinoline (0.3 mg/kg). Out of used compounds (1 mg/kg) isolated from Stephania, fangchinoline, fangchinoline 2'-N-alpha-oxide and 2'-N-norfangchinoline, which are substituted with 7-hydroxy side chain for 7-O-methyl side chain, decreased to near 50% of high blood glucose level. In addition, tetrandrine 2'-N-beta-oxide, tetrandrine 2'-N-alpha-oxide, tetrandrine 2-N-beta-oxide, fangchinoline 2'-N-alpha-oxide, which are added to 2- or 2'-N-oxide side chain, also decreased to near 50% of the high blood glucose level. In conclusion, fangchinoline but not tetrandrine from Stephania shows the anti-hyperglycemic action in the STZ-diabetic mice. The demethylation of 7-O-position and/or addition of 2- or 2'-N-oxide side chain in bis-benzylisoquinoline compounds in Stephania have a role for the induction of the anti-hyperglycemic actions.

Alkaloids↗

Pharmacological properties of traditional medicine (XXX): effects of Gyokuheifusan ([Symbol: see text]) on murine antigen-specific antibody production.

In the theory of traditional Chinese medicine (TCM), eqi ([Symbol: see text]) circulates at the superficial portion of the body to guard against exopathogen. Gyokuheifusan (GHS; [Symbol: see text]), containing Astragalus Root, Atractylodes Rhizome, and Saposhnikovia Root, is a TCM formula to treat the insufficiency of eqi by invigorating qi and consolidating the superficial resistance. In this study, we evaluated the effect of GHS on murine antibody production against ovalbumin (OVA) used as exopathogen. Balb/c mice were sensitized with OVA and alum via intraperitoneal (i.p.) injection or intranasal (i.n.) infusion daily for 7 d. GHS was orally administered daily at the dose of 10-times amount of human daily dosage from 3 d before the sensitization for 14 d. Fourteen d after the final sensitization, the blood was collected, and the concentrations of OVA-specific or non-specific immunoglobulins were measured. When OVA was sensitized i.p., the concentration of OVA-specific IgG, IgG1, IgG2a and IgA in the sera significantly increased by GHS-treatment. When OVA was sensitized i.n., GHS significantly reduce the concentration of OVA-specific IgG and IgG1 in the sera. Non-specific immunoglobulins were not changed by GHS-treatment. It is suggested that GHS could stimulate immune responses when antigen had already been invaded into the inside of the body, and that GHS might consolidate the resistance of nasal mucosa to protect from the invasion of OVA, then OVA-specific antibodies in sera might be hypocritically suppressed. The present study might provide the experimental evidence for TCM theory.

Animals↗

Rhizosphere-induced selenium precipitation for possible applications in phytoremediation of se polluted effluents.

Two bacterial isolates were obtained in axenic culture from the rhizosphere soil of Astragalus bisulcatus, a legume able to hyperaccumulate selenium. Both strains resulted of particular interest for their high resistance to the toxic oxyanion SeO3(2-) (selenite, Se(IV)). On the basis of molecular and biochemical analyses, these two isolates were attributed to the species Bacillus mycoides and Stenotrophomonas maltophilia, respectively. Their capability in axenic culture to precipitate the soluble, bioavailable and highly toxic selenium form selenite to insoluble and relatively non-toxic Se(0) (elemental selenium) was evaluated in defined medium added with 0.2 or 0.5 mM Se(IV). Both strains showed to completely reduce 0.2 mM selenite in 120 h, while 0.5 mM Se(IV) was reduced up to 67% of the initial concentration by B. mycoides and to about 50% by S. maltophilia in 48 h. Together in a dual consortium, B. mycoides and S. maltophilia increased the kinetics of selenite reduction, thus improving the efficiency of the process. A model system for selenium rhizofiltration based on plant-rhizobacteria interactions has been proposed.

Animals↗

Immunomodulating Chinese herbal medicines.

Traditional Chinese medicine always pays close attention to the strengthening of the patient's general resistance against illness, there are many Chinese herbs used for thousands of years are considered as tonics. Animal experiments and modern clinical trails have shown that quite a number herbs are immunologically active, and most of the tonics are excellent immunomodulating agents, such as polysaccharides or saponins isolated from Astragalus mongholicus, Acanthopanax senticosus and Panax notoginseng, which stimulated macrophages, promoted antibody formation, activated complement and increased T lymphocyte proliferation. Moreover, some of them were proved to be anti-irradiative and protected animals from liver intoxications. On the other hand, some anti-inflammative or anti-pyretic herbs such as Tripterygium wilfordii, Aconitum and Artemisiae species were proved to have immunosuppressive principles, some of them were now used clinically for the treatment of rheumatoid arthritis, chronic nephritis, systemic lupus erythematosis and various skin disorders. Pharmacological studies revealed that they have depressant effect on most of the humoral-immunity but not on the cell-mediated immunity. Some of them stimulated adrenal cortex functions and prolonged the survival time of transplanted allograft tissues.

Adjuvants, Immunologic↗

Chemometric classification of traditional Chinese medicines by their geographical origins using near-infrared reflectance spectra.

Some raw materials that have different places of production for the plant sources of the drugs Astragalus membranaceus and ginseng have been studied, based on their near-infrared reflectance spectra. The experimentally recorded spectra represent heavily ill-posed and highly correlative data sets. Three related methods, i.e. the Fisher linear discriminant analysis (FLDA), the ridge-type linear discriminant analysis (RLDA) and a newly proposed penalized ridge-type linear discriminant analysis (PRLDA), have been investigated. FLDA over-fits for the training objects of the two data sets to a high extent and is unstable for the predictive objects of the two data sets. RLDA shows obvious improvement in terms of over-fitting and unstability, but the stability for the predictive objects of the two data sets is too sensitive to their ridge-type penalized weights, tending to produce erroneous discrimination results. The proposed PRLDA can circumvent the two aforementioned problems with a large domain of penalized weights for correct discriminant analysis of the two data sets studied. The combination of the PRLDA method and near infrared reflectance spectroscopy can be adapted for the discrimination of the production places of plant sources of these drugs.

Algorithms↗

Immunomodulatory and antimicrobial effects of some traditional chinese medicinal herbs: a review.

The current practice of ingesting phytochemicals to support the immune system or to fight infections is based on centuries-old tradition. We review reports on seven Chinese herbs, (Aloe vera Mill. (Aloaceae), Angelica species (Umbelliferae), Astragalus membranaceus Bunge. (Leguminosae), Ganoderma lucidum (Fr.) Karst. (Ganodermataceae), Panax ginseng C.A Mey. (Araliaceae), Scutellaria species (Lamiaceae) and Zingiber officinale Rosc. (Zingiberaceae) with emphasis to their immunomodulatory and antimicrobial activities. While some of these herbaceous plants have a direct inhibitory effect on microbial organisms, we observe that each plant has at least one compound that selectively modulates cells of the immune system. The successful derivation of pure bioactive compounds from Ganoderma lucidum, ginseng and Zingiber officinale supports the traditional practice of using these plants to stimulate the immune system. As many modern drugs are often patterned after phytochemicals, studying the influence of each compound on immune cells as well as microbes can provide useful insights to the development of potentially useful new pharmacological agents.

Animals↗

Natural plant toxicants in milk: a review.

Elimination of plant toxicants via milk by lactating animals is considered a minor route of excretion; however, it may be important when the health of the neonate or food safety in humans is considered. Among plant toxicants excreted in milk is tremetol or tremetone, the toxin in white snakeroot (Eupatorium rugosum) and rayless goldenrod (Haplopappus heterophyllus). These plants have been responsible for intoxication of cows and their suckling calves and for many human poisonings. Other plant toxins excreted through the milk that pose a toxicity hazard include pyrrolizidine alkaloids in Senecio, Crotalaria, Heliotropium, Echium, Amsinckia, Symphytum (comfrey), Cynoglossum (hounds tongue) and Festuca (tall fescue); piperidine alkaloids in Conium, tobacco and others; quinolizidine alkaloids in Lupinus; sesquiterpene lactones of bitterweed and rubber weed; and glucosinolates in Amoracia (horseradish), Brassica (cabbage, broccoli, etc.), Limnanthes (meadowfoam), Nasturtium (watercress), Raphanus (radish) and Thlaspi (stinkweed). Many plants such as Astragalus, Oonopsis, Stanleya, Xylorrhiza, Aster, Atriplex, Sideranthus and Machaeranthera accumulate selenium and may cause intoxication when grazed. Selenium is found in the milk at concentrations relative to the amounts ingested by the lactating animal. Excretion of selenium via the milk is important in the deficiency state, but when in excess it may cause toxicity to offspring.

Animals↗

Feed preferences and habituation of sheep poisoned by locoweed.

Livestock addiction to locoweed is commonly cited as a clinical sign of locoweed poisoning. However, there have been no physiological or pathological explanations for the reported addiction. Four hypotheses were tested to evaluate locoweed's (Astragalus lentiginosus) addictive nature: 1) animals become psychologically addicted to locoweed; 2) animals have an innate preference for locoweed; 3) animals become habituated to locoweed in the sense of acquiring an acceptance or liking for it; and 4) intoxicated animals lose the ability to discriminate between feeds and eat whatever is present. Two feeding trials were conducted to evaluate these hypotheses. In 1987, 20 ewes were fed a pelleted basal feed consisting of alfalfa with 20% locoweed to induce locoweed poisoning. Five control ewes were fed pelleted alfalfa. In 1988, seven ewes were fed a basal feed consisting of alfalfa and 15% locoweed, and five control ewes were fed pelleted alfalfa. At 2- to 3-wk intervals, ewes from both trials were placed on cafeteria trials and offered a choice of four feeds (100% locoweed pellets, 15% or 20% locoweed pellets, mixed grain pellets and alfalfa pellets) to evaluate their preferences at increasing levels of intoxication. Sheep did not seek out locoweed, which would have indicated a psychological addiction. Locoweed was not innately palatable to sheep. One ewe habituated to 100% locoweed and two ewes habituated to the 15% locoweed diet. The rest of the ewes rejected the 100% locoweed pellets and the 15% or 20% locoweed basal feed when the choice of feeds was offered, even though they were severely intoxicated. Sheep show neither initial preference nor addiction to locoweed but may acquire preference (habituation).

Animal Feed↗

Ultrasound studies of the effects of certain poisonous plants on uterine function and fetal development in livestock.

Ingestion of locoweed (Astragalus spp. and Oxytropis spp.) by pregnant livestock may result in fetal malformations, delayed placentation, reduced placental and uterine vascular development, hydrops amnii, hydrops allantois, abnormal cotyledonary development, interruption of fetal fluid balance, and abortion. Ultrasonography of pregnant sheep fed locoweed demonstrated that abortion was first preceded by changes in fetal heart rate and strength of contraction and structural changes of the cotyledons, followed by increased accumulation of fetal fluid within the placental membranes and death of the fetus. During pregnancy the toxic agent in locoweed (swainsonine) apparently passes through the placental barrier to the fetus and during lactation through the milk to the neonate. Poison-hemlock (Conium maculatum), wild tree tobacco (Nicotiana glauca), and lunara lupine (Lupinus formosus) all contain piperidine alkaloids and induce fetal malformations, including multiple congenital contractures and cleft palate in livestock. Ultrasonography studies of pregnant sheep and goats gavaged with these plants during 30 to 60 d of gestation suggests that the primary cause of multiple congenital contractures and cleft palate is the degree and the duration of the alkaloid-induced fetal immobilization.

Animals↗

Pasture management strategies for reducing the risk of legume bloat in cattle.

Results from two decades (1973-1993) of bloat research at Kamloops are reviewed. The trials were conducted with groups of ruminally fistulated cattle either grazing or fed daily fresh-cut alfalfa (Medicago sativa) herbage. Studies were conducted during the growing season (May to September) and in the fall (October and November). The alfalfa was usually in the vegetative to early bloom stages of growth. Visual assessments of bloat severity on a scale of 1 to 5 were made .5 to 2 h after feeding started, at which time ruminal cannulas were opened to relieve ruminal pressure. Every cultivar of alfalfa tested caused bloat, but sainfoin (Onobrychis viciifolia), birdsfoot trefoil (Lotus corniculatus), and cicer milkvetch (Astragalus cicer) did not. This confirms the bloat-safe features of these alternate legume forages. Bloat was positively associated with the level of Fraction 1 protein and total soluble protein in alfalfa, supporting the concept of a decreased probability of bloat with advancing stages of plant maturity. There was no association between alfalfa saponins and bloat. Prefeeding ruminal chlorophyll levels were higher and ruminal clearance rates were lower in cattle that were susceptible to bloat. Cattle that bloated on a given day consumed 18 to 25% less alfalfa immediately before bloat than non-bloaters did in the same time period. Ruminal cations were associated with bloat incidence but cation manipulation through supplementation did not prevent bloat. Of all the feed additives tested, only poloxalene (Bloat Guard) completely prevented bloat.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗

Lack of maternal influence of lamb consumption of locoweed (Oxytropis sericea).

Locoweeds (Oxytropis and Astragalus spp.) are toxic plants found on many rangelands. Preferences for locoweed are learned; livestock often initially reject the plant, but learn to eat locoweed after continued exposure. Maternal influences are important in shaping diet selection in young animals. We studied the influence of ewe consumption of locoweed on lamb selection of the plant. Twenty-four ewes were divided into three treatment groups (n = 8): 1) ewes conditioned to eat locoweed (Oxytropis sericea) and avoid sodgrass (Poa pratensis) (Loco+Sod-); 2) ewes conditioned to avoid locoweed and eat sodgrass (Loco-Sod+); and 3) ewes conditioned to eat sodgrass and not exposed to locoweed (Loco0Sod+). A control group (n = 8) was composed of orphan lambs with no maternal influence (Orphans). All ewes were exposed to locoweed and(or) sodgrass without their lambs for 1 wk. Lambs were exposed to either locoweed or sodgrass with ewes for 5 min/d for 6 d. After weaning, lambs were tested for preferences by offering both locoweed and sodgrass for 3 min/d for 5 d; lambs were then offered only locoweed for 5 min/d for 5 d. Sodgrass was preferred by lambs. Lambs in the Loco+Sod- treatment group tended (P = .06) to take more bites of locoweed than lambs in the Loco0Sod+ group. Also, lambs in the Loco0Sod+ and Loco-Sod+ groups tended (P = .07) to take fewer locoweed bites compared with Orphans. Even though these results tended towards significance, the magnitude of the effect was small. There were no treatment effects when locoweed was offered alone. Although exposure with the mother did not strongly influence lambs to eat (or avoid) locoweed, all lambs ate some locoweed during testing. Short-term maternal influence does not seem to be sufficient to condition a preference for locoweed in lambs.

Animals↗

Teratogens in plants.

Many compounds synthesized by plants are known to be teratogenic in laboratory animals, but only a few have been shown by feeding trials to produce terata in livestock. Studies of plant teratogens affecting livestock have not moved forward in a systematic nor rapid way because of the logistical problems connected with such experiments in large animals. Information that has accumulated can be conveniently separated into three categories: (1) known teratogens in known teratogenic plants, (2) known teratogenic plants with unidentified teratogens, and (3) suspected teratogenic plants. Included in the first group are the teratogens from Lupinus, Veratrum, Conium and Leucaena genera; in the second group are included the Astragalus , Nicotiana and Trachymene genera; and in the third group are included Datura, Prunus , Sorghum and Senecio genera. Total available information in each case varies, but in a few instances considerable fundamental as well as practical information is now known. Research has provided enough information in a few instances to enable elimination of the practical problem or significant reduction in incidence.

Abnormalities, Drug-Induced↗