Intoxicación por Karwinskia Johnstonii / Intoxication by karwinskia johnstonii

El género Karwinskia (Rhamnaceae) incluye alrededor de 15 especies de árboles y arbustos cuyo hábitat natural va del sur de los Estados Unidos de Norteamérica al norte de Colombia y el Caribe. En la República Mexicana se han identificado once especies las que, con excepción de K. Johntonii y K. tehuacana, han sido objeto de estudios botánicos, químicos y toxicológicos, teniéndose, además, en el caso específico de K. humboldtiana, diversos estudios clínicos. De K. johnstonii Fernández solamente se tenían referencias acerca de su descripción botánica, distribución geográfica, nombres comunes uso medicinal atribuido a sus hojas. En este trabajo se incluyen 12 casos de parálisis o paresia fláccidad atendidos en el Hospital Infantil de Morelia, en los que logró identificarse como agente causal a K. johnstonii Fernández. Tales casos forman parte de un ancestral y grave problema regional de salud pública para los estados de Michoacán y Guerrero, respectivamente

Comprovacao quimica e biologica da presenca de monofluoroacetato nas folhas de Palicourea marcgravii St. Hil. / Chemical and biological confirmation of the presence of monofluoroacetate in the leaves of Policourea marcgravii St. Hil.

Palicourea marcgravii St. Hil. (Rubiaceae) vulgarmente conhecida como "erva de rato" e uma planta toxica brasileira de grande interesse economico na pecuaria, por provocar, em bovinos, convulsoes, arritmias cardiacas e "morte subita" em elevado numero de animais. No presente trabalho, as folhas dessecadas e moidas de P.marcgravii foram extraidas com etanol 95//, a temperatura ambiente, por percolacao; o extrato resultante foi fracionado por particao com acetato de etila e butanol saturado com agua. Os residuos obtidos foram testados "per os" em ratos, buscando-se investigar nos mesmos, a presenca do principio ativo toxico. O residuo aquoso foi o unico que produziu convulsoes e morte dos animais. A existencia do monofluoroacetato (MFA) no residuo aquoso foi comprovada biologicamente atraves do paralelismo entre as retas referentes as funcoes dose/porcentagem de letalidade e dose/latencia para a primeira convulsao que foram construidas para o residuo aquoso e padrao de referencia (monofluoroacetato de sodio). O MFA foi tambem identificado quimicamente atraves da RMN'ANT.POT.19F' e da cromatografia em camada delgada. Os resultados obtidos comprovaram a presenca de MFA nas folhas de P.marcgravii, responsabilizando-o pelos efeitos toxicos produzidos. Tambem foram levantadas algumas hipoteses na tentativa de explicar a sintomatologia dos animais intoxicados

Variación del contenido de cianuro en Prunus brachybotrya en la segunda mitad de su desarrollo / Cyanide content variation in Punus brachybotrya at ists second stage development

El aguacatillo (Prunus brachybotrya) es una planta que perteneca al género de los Prunus y familia de las rosáceas. Puede contener ácido cianhídrico en las hojas, tallo y fruto; si es consumida por el ganado es letal. Se desarrolla y fructifica en laqs faldas de los volcanes Popocatepetl e Ixtaccihuatl. En el presente tranajo se analizó in vitro el contenido de cianuro del aguacatillo en hojas, tallo y fruto por la técnica de Steyn modificada. El muestreo se realizó de marzo a julio de 1989, con intervalos de 15 días entre una muestra y otra. En las primeras tres muestras, la concentración de cianuro aumentó en laqs tres partes de la planta (hoja, fruto y tallo). En la hoja, a partir de mayo, la concentración de cianuro empezó a disminuir. En julio, la concentración de cianuro en el fruto bajó a cero; en el tallo, bajó ligeramente. Las concentraciones fueron de 1.7 porciento en la hoja y fruto; en el último, declinó hasta cero al 5to mes durante la maduración, En el tallo tierno, la concentración due fe 0.25 porciento; durante el estudio, se mantuvo en este nivel. El aguacatillo se considera más peligroso en los meses de abril a mayo, ya que durante este periodo la concentración de cianuro es mayor. Así, la intoxicación se intensifica más que en los otros meses, aunque està presente todo el año.

Photosensitivity in South Africa. VI. The experimental induction of geeldikkop in sheep with crude steroidal saponins from Tribulus terrestris.

Geeldikkop was induced in sheep by the oral administration of crude steroidal saponins from Tribulus terrestris. Two of the sheep developed typical lesions of geeldikkop, including birefringent crystalloid material in bile ducts and concentric periductal lamellar fibrosis. The clinical pathological changes in these sheep were also consistent with those of geeldikkop: aspartate transaminase and gamma-glutamyl transferase activities in the sera of both were elevated, and one had bilirubinaemia. A third sheep became photosensitive without typical lesions of geeldikkop in the liver or changes in the activities of liver enzymes before euthanasia. The findings of these trials are consistent with reports from abroad that ovine hepatogenous photosensitization, caused by Agave lechuguilla and Narthecium ossifragum, can be induced with crude saponins from the respective plants.

Hepatotoxic and nephrotoxic principles in Terminalia oblongata.

A study was conducted to identify and characterise the toxic principle in Terminalia oblongata, commonly known as yellow-wood. Crude aqueous extracts of yellow-wood leaf were found to produce the same liver lesion in mice as has been reported in ruminants. The hepatotoxic fraction was isolated and identified as a hydrolysable vegetable tannin called punicalagin. When given orally, the dose required to produce toxicity was at least 20 times greater than when given intraperitoneally. Following a given dose of punicalagin, the onset and severity of liver necrosis was found to be related to the time interval after dosing. In addition to punicalagin, an unidentified nephrotoxic substance was found which was capable of producing avascular renal necrosis without liver necrosis.

Studies on the preparative capability of the horizontal flow-through coil planet centrifuge and high-performance liquid chromatography in the separation of polar compounds from Oxytropis ochrocephala Bunge.

Horizontal flow-through coil planet centrifuge (CPC) and high-performance liquid chromatography (HPLC) techniques were used for separation of polar compounds from a crude ethanol extract of Oxytropis ochrocephala Bunge, a poisonous legume plant widely distributed in northwestern China. The performance of these two chromatographic methods was compared in terms of column efficiency, peak resolution, separation time, sample loading capacity, etc. The results indicated that two polar compounds in the crude extract were equally well separated by these two methods. HPLC gave comparable peak resolution in shorter separation time while its sample loading capacity was limited to the mg range. The CPC method required a long separation time, but yielded a higher purity of fractions with a much greater capacity.

Contact urticaria due to the common stinging nettle (Urtica dioica)--histological, ultrastructural and pharmacological studies.

A frequent cause of contact urticaria is skin exposure to the common stinging nettle (Urtica dioica). The urticaria is accompanied by a stinging sensation lasting longer than 12 h. Little is known of the cellular and molecular mechanism of stinging-nettle urticaria. After preliminary pharmacological analysis of pro-inflammatory activity in nettle stings, the cellular response of mononuclear cells, polymorphonuclear cells and mast cells was examined in six people 5 min and 12 h after nettle contact. Only mast cell numbers were significantly increased at 12 h. Ultrastructurally, some mast cells showed evidence of degranulation at 5 min and 12 h. At 12 h mast cells were closely associated with dermal dendritic cells and lymphocytes suggesting a functional unit. The mean histamine and serotonin contents of a nettle hair were found to be 6.1 ng and 33.25 pg, respectively. Nettle-sting extracts did not demonstrate histamine release from dispersed rat mast cells in vitro. These results suggest that part of the immediate reaction to nettle stings is due to histamine introduced by the nettle. However, the persistence of the stinging sensation might suggest the presence of substances in nettle fluid directly toxic to nerves or capable of secondary release of other mediators.

[Flavonoid constituents of Melicope triphylla MERR.II].

From the leaves of Melicope triphylla MERR., three new flavonoids (1-3) were isolated, together with nine known flavonoids, 4',5-dihydroxy-3,3',7- trimethoxyflavone (4), 5-hydroxy-3,3',4',7-tetramethoxyflavone (5), 3,3',4',5,7-pentamethoxyflavone (6), 7-hydroxy-3,3',4',5,8-pentamethoxyflavone (7), 3,3',4',5,7,8-hexamethoxyflavone (8), 5-hydroxy-3,7,8-trimethoxy-3',4'-methylenedioxyflavone (9), 7-hydroxy-3,5,8- trimethoxy-3',4'-methylenedioxyflavone (10), 3,5,7,8-tetramethoxy-3',4'-methylenedioxyflavone (11), and 5-hydroxy- 3,6,7,8-tetramethoxy-3',4'-methylenedioxyflavone (12). The structures of 1, 2, and 3 were established as 5-hydroxy-3,7-dimethoxy-3',4'-methylenedioxyflavone, 5-hydroxy-7-isopentenyloxy-3,8-dimethoxy-3',4'-methylenedioxyfl avone, and 4'-hydroxy-7-isopentenyloxy-3,3',5,8-tetramethoxyflavone by their respective chemical and spectral data. The 20 flavonoids isolated from this plant were examined for the piscicidal activities.

Prevention of hydrolysable tannin toxicity in goats fed Clidemia hirta by calcium hydroxide supplementation.

Although plants containing hydrolysable tannins can be hepatotoxic, such poisoning has not been reported in Indonesia despite the presence of these plants. In order to determine the hepatotoxic potential of Indonesian plants, goats were intoxicated experimentally with the Indonesian plant Climedia hirta (harendong), which contained 19% hydrolysable tannin. The prophylactic effect of Ca(OH)2 supplementation on the disease was also examined. Two groups of goats were fed for 28 days with grain-based pellets containing 50% harendong leaf or 50% harendong leaf + 8% Ca(OH)2. Two control groups were fed similar pellets containing 50% of the non-toxic elephant grass (Pennisetum purpureum) with and without 8% Ca(OH)2. Serum enzymes indicative of liver damage were monitored during the experiment and histopathological examination of selected tissues was done at the conclusion of the experiment. In goats given unsupplemented harendong pellets there was a significant increase in aspartate aminotransferase and glutamate dehydrogenase from 50.2 and 20.6 U l-1 to 219.6 and 63.3 U l-1, respectively. These changes were associated with moderate to severe nuclear plemorphism, vacuolation and megalocytosis of hepatocytes and deposits of brown pigment in the Kupffer cells. There was also nephrosis of the renal convoluted tubules and collecting ducts, abomasitis and enteritis. Biochemical and histological changes were reduced significantly in the harendong + Ca(OH)2 group and virtually absent from control groups. It is concluded that hydrolysable tannins in harendong leaf are hepato- and nephrotoxic and associated with gastroenteritis, but that poisoning may be ameliorated by Ca(OH)2 supplementation.

The in vivo erythrocyte micronucleus test: measurement at steady state increases assay efficiency and permits integration with toxicity studies.

The mouse erythrocyte micronucleus assay has been traditionally carried out using one or two exposures to the test agent, followed by sampling at two or three postexposure times to obtain a sample near the time of the transient peak of micronucleated polychromatic erythrocytes (PCEs). We have demonstrated that frequencies of micronucleated RNA-positive (PCEs) and RNA-negative erythrocytes in blood and bone marrow come to steady state during "continuous" exposure via diet or drinking water, or during repeated daily exposures to test agents by ip injection, gavage, or inhalation. Under these exposure conditions, frequencies of micronucleated cells in peripheral blood approached steady state within 2-3 days in RNA-positive erythrocytes and in 5-6 weeks in RNA-negative erythrocytes. With exposure durations of 6 days (monocrotaline or Crotalaria seeds in diet), 10 days (triethylenemelamine, mitomycin C, 7,12-dimethylbenzanthracene, or colchicine, ip daily), 90 days (triethylenemelamine or urethan in drinking water or 1,3-butadiene via inhalation), or 2 years (benezene by daily gavage), frequencies of micronucleated cells attained and remained at steady state for prolonged periods. At steady state, frequencies of micronucleated RNA-positive cells in bone marrow samples were similar to those in RNA-positive and RNA-negative cells in peripheral blood (e.g., triethylenemelamine in drinking water at 4 micrograms/ml resulted in frequencies of micronucleated RNA-negative erythrocytes in peripheral blood of 27/1000 after 45 days of exposure and 24/1000 after 90 days, with a frequency of 28/1000 in bone marrow RNA-positive erythrocytes after 90 days). The data suggest that the efficiency of the assay would be markedly improved by using a repeated dose schedule with a single sample taken at steady state, rather than scoring multiple samples at various times after a single dose. This approach allows the frequency of micronucleated cells to be measured in a sample of bone marrow or blood obtained at almost any stage of routine toxicity testing.

Two toxic kaurene glycosides from the burrs of Xanthium pungens.

Two H2O-soluble toxic kaurene glycosides 3 and 4 responsible in part for the poisonous properties of the burr of Xanthium pungens have been isolated and identified. The structures of the compounds were elucidated using high resolution 2D nmr and mass spectral techniques.

Characterization of the anticoagulant activities from a Brazilian arrow poison.

A recent report indicated that an arrow poison used by the native Indians of Rondonia, Brazil, to kill small animals was associated with profuse bleeding. The arrow poison was prepared from the bark of a tree, known locally as Tike-Uba. We have obtained bark and sap specimens from this tree and have characterized a potent anticoagulant activity in both the crude bark and sap samples as well as in more highly purified preparations. An aqueous extract of the bark significantly prolongs both prothrombin times and activated partial thromboplastin times in plasma based assays. Further fractionation of the bark extract and sap by molecular weight indicated that all of the anticoagulant activity could be isolated in a molecular weight fraction of equal to or greater than 30,000 daltons. The anticoagulant activity was also further purified by C-18 reverse phase chromatography. When highly purified preparations of the anticoagulant activity from the Tike-Uba tree were examined in specific blood coagulation enzyme assays utilizing chromogenic substrates, the highest inhibitory potency was found versus thrombin, followed by factor Xa. These studies establish the presence of a compound(s) in a Brazilian arrow poison, which potently disrupts mammalian blood clotting, and which may account for some of the observed toxicities associated with the arrows.

Immunoreactive leukotrienes in nettle plants (Urtica urens).

In order to clarify the mechanisms of urtication after contact with stinging plants, nettle (Urtica urens) hair and whole-plant extracts were examined for the presence of leukotriene (LT) B4 and LTC4 by reverse phase high-pressure liquid chromatography (RP-HPLC) and radioimmunoassay (RIA) and for in vitro neutrophil chemotactic activity and histamine contents. Both hair and plant extracts contained high levels of LTB4 and LTC4 by RIA as well as histamine. The presence of LTB4 was supported by RP-HPLC elution profiles and by in vitro chemotaxis. Nettle hairs therefore resemble insect venoms and cutaneous mast cells with regard to their spectrum of mediators.

Skin and liver toxicity in experimental Lantana camara poisoning in albino rats.

Dried alcoholic extract of fresh Lantana camara leaves (LE), on oral administration to albino rats of both sexes, induced photodermatitis during exposure to clear sunlight for 1 hr. Its severity was related to the dose of LE and was maximal in rats exposed to sunlight from 4 to 14 hr after feeding LE and gradually declined over 40 hr. Wavelengths of light about 540 to 570 mu only were effective. In control study, the alcoholic extract of edible spinach leaves was only 1/3 in potency and its effect lasted for less than 20 hr. LE did not raise serum bilirubin, SGOT, SGPT or cause liver injury as assessed by light microscopy. However, like CCL4 but unlike spinach extract, LE impaired excretion of BSP by liver, proportionate to the dose and also maximal at 5.5 hr declining thereafter over 40 hr.

A new toxic neoanisatin derivative from the pericarps of Illicium majus.

A new toxic neoanisatin-derivative (1) was isolated from the pericarps of Illicium majus. The structure of this compound was elucidated by spectroscopic data, including the 2D COSY NMR technique. The toxicity of compound 1 is also described.

Spirosolane-containing Solanum species and induction of congenital craniofacial malformations.

Comparison by GC analysis of purified alkaloid extracts of Solanum species revealed no measurable free solasodine, other spirosolanes, or any non-spirosolane steroidal alkaloid aglycones in unhydrolyzed total alkaloid fractions of fruit of Solanum elaeagnifolium Cav. (silverleaf nightshade), Solanum sarrachoides (S. villosum Lam.--hairy nightshade), Solanum dulcamara L. (European bittersweet nightshade) or Solanum melongena L. (eggplant). All alkaloidal material was apparently present as glycoside. Conversely, sprouts of Solanum tuberosum L. (potato) contained 67% of its alkaloids as glycosides, which was freed only upon hydrolysis with the remaining 33% present as free solanidine. GC/MS analysis of hydrolysates of purified extracts of the test Solanum species revealed that solasodine was a principal or sole aglycone of the alkaloid glycosides in each of the test species except Solanum tuberosum. In the latter, solanidine was the sole aglycone. Among the test species, exclusive of S. tuberosum, only S. dulcamara contained aglycones other than solasodine. In addition to solasodine, S. dulcamara contained appreciable amounts of an unknown spirosolane, an aglycone provisionally identified as soladulcidine. The induction of congenital craniofacial malformations in hamsters by high oral doses of the four Solanum species that contained mainly solasodine glycosides--S. elaeagnifolium, S. dulcamara, S. sarrachoides and S. melongena was compared to inductions of malformations by Solanum tuberosum, that contained mainly solanidane glycosides. Compared to controls, Solanum elaeagnifolium and Solanum dulcamara fruit both induced a high percentage incidence of deformed litters (20.4 and 16.3, respectively) that was statistically significant (P less than 0.001 level) while percentage incidence of deformed litters induced by Solanum sarrachoides and Solanum melongena fruit (9.5 and 7.6 respectively) were both higher than controls (3.4%), in neither case was the incidence statistically significant (P less than .05). Deformed litter incidence induced by sprouts of Solanum tuberosum was 24.0%, (P less than 0.001).