Hydrallantois in cows naturally poisoned by Sida carpinifolia in Brazil.

Sida carpinifolia is a small subshrub that is distributed throughout Brazil and is responsible for lysosomal storage disease and occasional reproductive problems in cattle, goats, equids, sheep, and deer. We describe herein the clinical, epidemiologic, and pathologic features of hydrallantois in 3 cows naturally poisoned by S. carpinifolia in Rio Grande do Sul State, Brazil. Clinically, all cows had marked abdominal distension and mild ataxia. After natural death or euthanasia, autopsies revealed that the abdominal distension in all 3 cases was caused by severe enlargement of the uterus, which contained 100-120 L of translucent fluid within the allantois, in addition to adventitial placentation. Microscopic evaluation of the placenta revealed marked diffuse edema, sometimes with a myxomatous appearance. Neurons in the cerebellum and obex were swollen, with mild-to-moderate cytoplasmic granular vacuolation. Histochemical examination with lectins ConA, WGA, and sWGA revealed mild-to-marked staining in the cytoplasm of neurons of the cerebellum and medulla at the level of the obex, indicating the occurrence of α-mannosidosis.

Primary photosensitization and contact dermatitis caused by Malachra fasciata Jacq. N.V. (Malvaceae) in sheep.

Farmers from Paraiba state, Northeast Brazil, claim that Malachra fasciata causes cutaneous lesions in sheep. To test its toxicity the plant was harvested daily and fed ad libitum for 21 days to 3 sheep as the sole food source (# 1-3). An additional sheep (# 4) was maintained as a control. Cutaneous lesions of photosensitization initiated after 7 days and increased continuously over the next 21 days. The dose ingested varied between 129 g/kg to 175 g/kg. Alopecia, hyperemia and crusting were observed in the animals. On day 22, sheep 3 was euthanized. At necropsy, no gross or microscopic alterations were observed in the liver. Skin biopsies were performed in the remaining animals Histopathology of skin of the three sheep included acanthosis, orthokeratosis, and multifocal infiltration by lymphocytes, eosinophils and plasma cells around blood vessels and appendages in the dermis. The Splendore-Hoeppli phenomenon was observed in the dermis of sheep 2, due probably by contact dermatitis. After the end of administration Sheep 1 and 2 were protected from sunlight and the lesions regressed within two weeks. This experiment indicates that M. fasciata causes primary photosensitization and contact dermatitis in sheep.

Spontaneous poisoning by Sida carpinifolia (Malvaceae) in horses / Intoxicação natural por Sida carpinifolia em equinos

Sida carpinifolia poisoning causes a chronic neurodegenerative disorder associated with lysosomal storage by indolizidine alkaloids (swainsonine). The epidemiological, clinical, pathological and lectin histochemistry findings of an outbreak of natural poisoning by S. carpinifolia in horses in Rio Grande do Sul state, Brazil, are described. Five horses from a total of 15 that were kept on native pasture with large amounts of S. carpinifolia presented during 90 days clinical signs of progressive weight loss, incoordination, stiff gait and ramble, in addition to exacerbated reactions and locomotion difficulty after induced movement. Four horses died, and one of them was submitted for necropsy. At necropsy, no significant gross lesions were observed. Histological findings observed in the central nervous system were characterized by swollen neurons with cytoplasm containing multiple microvacuoles; these abnormalities were more severe in the thalamus, hippocampus, cerebellum and pons. Using lectin histochemistry, the pons and hippocampus sections stained positive for commercial lectin Con-A, sWGA and WGA. This study aimed to detail S. carpinifolia poisoning in horses to be included in the differential diagnoses of neurological diseases of horses.(AU)

A intoxicação por Sida carpinifolia é uma desordem neurodegenerativa crônica associada ao acúmulo lisossomal pelo alcaloide indolizidínico, denominado swainsonina. Descrevem-se os achados epidemiológicos, clínicos, patológicos e de lectina-histoquímica de um surto de intoxicação natural por S. carpinifolia em equinos no Rio Grande do Sul, Brasil. De um total de 15 equinos, cinco equinos mantidos em campo nativo com grande quantidade de S. carpinifolia apresentaram sinais clínicos de emagrecimento progressivo, incoordenação, andar rígido e deambulação, além de dificuldade de locomoção com reações exacerbadas após estímulos ao movimento em um período de 90 dias de evolução clínica. Quatro equinos vieram a óbito e um foi submetido ao exame de necropsia. À necropsia, não foram observadas lesões macroscópicas. Os achados histológicos observados no sistema nervoso central caracterizaram-se por aumento de tamanho dos neurônios, com citoplasma contendo microvacúolos; tais alterações foram observadas com maior intensidade em tálamo, hipocampo, cerebelo e ponte. Na lectina-histoquímica, fragmentos de ponte e hipocampo marcaram positivamente para as lectinas comerciais Con-A, sWGA e WGA. Este trabalho visa alertar a ocorrência da intoxicação por S. carpinifolia em equinos, a qual deve ser incluída como diagnóstico diferencial dentre as doenças neurológicas de equinos.(AU)

Sida tuberculata (Malvaceae): a study based on development of extractive system and in silico and in vitro properties.

Sida tuberculata (Malvaceae) is a medicinal plant traditionally used in Brazil as an antimicrobial and anti-inflammatory agent. Here, we aimed to investigate the different extractive techniques on phytochemical parameters, as well as to evaluate the toxicity and antioxidant capacity of S. tuberculata extracts using in silico and in vitro models. Therefore, in order to determine the dry residue content and the main compound 20-hydroxyecdysone (20E) concentration, extracts from leaves and roots were prepared testing ethanol and water in different proportions. Extracts were then assessed by Artemia salina lethality test, and toxicity prediction of 20E was estimated. Antioxidant activity was performed by DPPH and ABTS radical scavenger assays, ferric reducing power assay, nitrogen derivative scavenger, deoxyribose degradation, and TBARS assays. HPLC evaluation detected 20E as main compound in leaves and roots. Percolation method showed the highest concentrations of 20E (0.134 and 0.096 mg/mL of extract for leaves and roots, respectively). All crude extracts presented low toxic potential on A. salina (LD50 >1000 µg/mL). The computational evaluation of 20E showed a low toxicity prediction. For in vitro antioxidant tests, hydroethanolic extracts of leaves were most effective compared to roots. In addition, hydroethanolic extracts presented a higher IC50 antioxidant than aqueous extracts. TBARS formation was prevented by leaves hydroethanolic extract from 0.015 and 0.03 mg/mL and for roots from 0.03 and 0.3 mg/mL on egg yolk and rat tissue, respectively (P<0.05). These findings suggest that S. tuberculata extracts are a considerable source of ecdysteroids and possesses a significant antioxidant property with low toxic potential.

Analysis of Swainsonine and Swainsonine N-Oxide as Trimethylsilyl Derivatives by Liquid Chromatography-Mass Spectrometry and Their Relative Occurrence in Plants Toxic to Livestock.

There are limited data concerning the occurrence of swainsonine N-oxide in plants known to contain swainsonine and its relative impact on toxicity of the plant material. A liquid chromatography-mass spectrometry method based on a solvent partitioning extraction procedure followed by trimethylsilylation and analysis using reversed phase high-pressure liquid chromatography-mass spectrometry was developed for the analysis of swainsonine and its N-oxide. The concentrations of each were measured in several swainsonine-containing taxa as well as two endophytic isolates that produce swainsonine. In vegetative samples the relative percent of N-oxide to free base ranged from 0.9 to 18%. In seed samples the N-oxide to free base ratio ranged from 0 to 10%. The measured concentrations of swainsonine N-oxide relative to swainsonine only slightly increases the actual toxicity of the various plant samples in a combined assay of both compounds.

Sida tuberculata (Malvaceae): a study based on development of extractive system and in silico and in vitro properties

Sida tuberculata (Malvaceae) is a medicinal plant traditionally used in Brazil as an antimicrobial and anti-inflammatory agent. Here, we aimed to investigate the different extractive techniques on phytochemical parameters, as well as to evaluate the toxicity and antioxidant capacity of S. tuberculata extracts using in silico and in vitro models. Therefore, in order to determine the dry residue content and the main compound 20-hydroxyecdysone (20E) concentration, extracts from leaves and roots were prepared testing ethanol and water in different proportions. Extracts were then assessed by Artemia salina lethality test, and toxicity prediction of 20E was estimated. Antioxidant activity was performed by DPPH and ABTS radical scavenger assays, ferric reducing power assay, nitrogen derivative scavenger, deoxyribose degradation, and TBARS assays. HPLC evaluation detected 20E as main compound in leaves and roots. Percolation method showed the highest concentrations of 20E (0.134 and 0.096 mg/mL of extract for leaves and roots, respectively). All crude extracts presented low toxic potential on A. salina (LD50 >1000 µg/mL). The computational evaluation of 20E showed a low toxicity prediction. For in vitro antioxidant tests, hydroethanolic extracts of leaves were most effective compared to roots. In addition, hydroethanolic extracts presented a higher IC50 antioxidant than aqueous extracts. TBARS formation was prevented by leaves hydroethanolic extract from 0.015 and 0.03 mg/mL and for roots from 0.03 and 0.3 mg/mL on egg yolk and rat tissue, respectively (P<0.05). These findings suggest that S. tuberculata extracts are a considerable source of ecdysteroids and possesses a significant antioxidant property with low toxic potential.

Occupational asthma caused by samba (Triplochiton scleroxylon) wood dust in a professional maker of wooden models of airplanes: a case study.

OBJECTIVES: Wood dust is a known occupational allergen that may induce, in exposed workers, respiratory diseases including asthma and allergic rhinitis. Samba (obeche, Triplochiton scleroxylon) is a tropical tree, which grows in West Africa, therefore, Polish workers are rarely exposed to it. This paper describes a case of occupational asthma caused by samba wood dust. MATERIAL AND METHODS: The patient with suspicion of occupational asthma due to wood dust was examined at the Department of Occupational Diseases and Clinical Toxicology in the Nofer Institute of Occupational Medicine. Clinical evaluation included: analysis of occupational history, skin prick tests (SPT) to common and occupational allergens, determination of serum specific IgE to occupational allergens, serial spirometry measurements, metacholine challenge test and specific inhalation challenge test with samba dust RESULTS: SPT and specific serum IgE assessment revealed sensitization to common and occupational allergens including samba. Spirometry measurements showed mild obstruction. Metacholine challenge test revealed a high level of bronchial hyperactivity. Specific inhalation challenge test was positive and cellular changes in nasal lavage and induced sputum confirmed allergic reaction to samba. CONCLUSIONS: IgE mediated allergy to samba wood dust was confirmed. This case report presents the first documented occupational asthma and rhinitis due to samba wood dust in wooden airplanes model maker in Poland.

Doença do armazenamento lisossomal induzida pelo consumo de Sida carpinifolia em bovinos do Rio Grande do Sul / Lysosomal storage disease caused by Sida carpinifolia in cattle in Rio Grande do Sul

This paper reports the natural poisoning by Sida carpinifolia (guanxuma, chá-da-índia) in cattle in Rio Grande do Sul, Brazil. Five cattle were affected in the period 2001-2008. Clinical signs included weight loss, incoordination, walking difficulty, generalized tremors, frequent falls, and death. Microscopically, the main changes were vacuolation of Purkinje neurons in the cerebellum, pancreatic acinar cells, and thyroid follicular cells. Transmission electron microscopy revealed vacuoles bordered by membrane containing finely granular material. Lectin histochemistry showed positive staining in neurons with the lectins Concanavalia ensiformis (Con-A), Triticum vulgaris (WGA), and Succinyl Triticum vulgaris (sWGA).

Relata-se a intoxicação natural por Sida carpinifolia (guanxuma, chá-da-índia) em bovinos no Rio Grande do Sul. Foram afetados cinco bovinos no período 2001-2008. O quadro clínico foi caracterizado por emagrecimento, incoordenação, dificuldade de locomoção, tremores generalizados, quedas frequentes e morte. Microscopicamente, as principais alterações foram vacuolização dos neurônios de Purkinje do cerebelo, das células acinares do pâncreas e das células foliculares da tireoide. A microscopia eletrônica evidenciou vacúolos com conteúdo finamente granulado e delimitado por membrana. Na lectina-histoquímica, observou-se marcação em neurônios com as lectinas Concanavalia ensiformis (Con-A), Triticum vulgaris (WGA) e Succinyl Triticum vulgaris (sWGA).

Alpha-mannosidase activity in goats fed with Sida carpinifolia.

Human alpha-mannosidosis results from alpha-mannosidase deficiency and progressive accumulation of mannose-rich oligosaccharides in lysosomes. Two days before Saanen goats were fed with Sida carpinifolia, alpha-mannosidase activity in leukocytes was 128+/-28 nmoles4-MU/h/mgprotein (first trial) and 104+/-6 nmoles4-MU/h/mgprotein (second trial). At day 5, after the introduction of S. carpinifolia diet, the alpha-mannosidase activity in leukocytes was significantly increased, both in the first (288+/-13 nmoles4-MU/h/mgprotein) and in the second trial (303+/-45 nmoles4-MU/h/mgprotein), and it returned to normal levels 2 days after the withdrawal of the plant from the diet (114+/-7 nmoles4-MU/h/mgprotein in first trial, and 108+/-25 nmoles4-MU/h/mgprotein in the second one). Plasma alpha-mannosidase activity decreased significantly 4 days after animal exposure to the S. carpinifolia diet (769+/-167 nmoles4-MU/h/ml) and returned to normal values 10 days after the withdrawal of the plant from the diet (1289+/-163 nmoles4-MU/h/ml). Thin-layer chromatography showed an abnormal excretion of oligosaccharides in urine as of day 2 after diet exposure, which persisted until one day after the withdrawal of the plant. Animals presented neurological clinical signs beginning at day 37 (in the first trial) and at day 25 (in the second trial) after being fed with the plant. The results obtained herein suggest that oligosaccharides observed in urine are a result of a decrease in alpha-mannosidase activity in plasma. S. carpinifolia seems to have other compounds that act on alpha-mannosidase enzyme in leukocytes in a competitive manner with swainsonine. The increase in alpha-mannosidase enzyme in leukocytes could be attributed to one of these compounds present in S. carpinifolia.

Intoxicação experimental por Sida carpinifolia (Malvaceae) em bovinos / Experimental poisoning by Sida carpinifolia (Malvaceae) in cattle

Descrevem-se os achados clínicos e patológicos da intoxicação experimental por Sida carpinifolia em bovinos. Para a reprodução experimental da doença, folhas verdes da planta foram coletadas semanalmente na região do Alto Vale do Itajaí e fornecidas in natura diariamente para cinco bovinos nas doses de 10 e 20g/kg por 120 dias, 40g/kg por 30 dias, e 30 e 40g/kg de peso animal por 150 dias. Um bovino morreu e os outros foram eutanasiados ao final do período de consumo da planta. Os principais sinais clínicos consistiam de andar em marcha, olhar atento e tremores de cabeça e foram de intensidade leve a acentuado conforme a dose de planta e tempo de consumo. A lesão histológica predominante caracterizava-se por vacuolização e tumefação de neurônios (principalmente os de Purkinje), das células acinares pancreáticas e células foliculares da tireóide. Ultra-estruturalmente verificou-se vacúolos, por vezes, contendo material finamente granular em neurônios, células acinares pancreáticas e células foliculares da tireóide. S. carpinifolia causa doença de depósito lisossomal em bovinos quando consumida por período prolongado, mesmo em pequenas doses.

Clinical and pathological findings of experimental poisoning by Sida carpinifolia in cattle are described. A neurologic disease was observed in cattle on farms of the Alto Vale do Itajaí region of the Brazilian state of Santa Catarina. For the experimental reproduction of the disease, fresh green leaves, weekly harvested in the same region where spontaneous case occurred, were force-fed to five cattle at doses of 10 and 20g/kg for 120 days, 40g/kg for 30 days, and 30 and 40g/kg body weight for 150 days. One animal died and the others were euthanatized at the end of the experiment. Clinical signs and lesions varied from mild to severe in the experimentally poisoned cattle and depended on dose and length of the period of consumption. Main histological and ultrastructural lesions consisted of vacuolation and distension of neuronal perikarya (mainly of Purkinje cells), and of the cytoplasm of acinar pancreatic cells and thyroid follicular cells. It is concluded that ingestion of even small amounts S. carpinifolia for prolonged periods of time cause lisosomal storage disease in cattle.

Pharmacological actions of Thespesia populnea relevant to Alzheimer's disease.

Thespesia populnea (Malvaceae) is a large tree found in the tropical regions and coastal forests of India. Various parts of T. populnea are found to possess useful medicinal properties, such as antifertility, antibacterial, anti-inflammatory, antioxidant, purgative and hepatoprotective activity. The present study was undertaken to investigate the effects of T. populnea bark on cognitive functions, total cholesterol levels and cholinesterase activity in mice. A total of 312 mice divided into 52 different groups were employed in the present investigation. The ethanolic extract of T. populnea (TPE) was administered orally in three doses (100, 200 and 400 mg/kg) for 7 successive days to different groups of young and aged mice. The learning and memory parameters were assessed using elevated plus maze and passive avoidance apparatus. TPE (200 and 400 mg/kg, p.o.) showed significant improvement in memory of young and aged mice. TPE also reversed the amnesia induced by scopolamine (0.4 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.). Furthermore, TPE reduced significantly the central (brain) cholinesterase activity in mice. TPE exhibited a remarkable cholesterol lowering property comparable to simvastatin (a standard drug) in the present study. Furthermore, we observed that, T. populnea bark possessed a powerful memory enhancing activity in mice. Since diminished cholinergic transmission and increased cholesterol levels appear to be responsible for development of amyloid plaques and dementia in Alzheimer patients, TPE may prove to be a useful medicine on account of its multifarious beneficial effects, such as memory improving property, cholesterol lowering, anticholinesterase and anti-inflammatory activity. Therefore, T. populnea bark appears to be a promising candidate for improving memory and it would be worthwhile to explore the potential of this plant in the management of Alzheimer patients.

Intoxicação experimental por Sida carpinifolia (Malvaceae) em ovinos / Experimental poisoning by Sida carpinifolia (Malvaceae) in sheep

Administrou-se Sida carpinifolia L.f. secada à sombra e moída, em doses diárias de 11 a 30g/kg/dia, para sete ovinos. Um animal foi encontrado morto aos 18 e outro morreu apresentando sinais clínicos aos 53 dias do início do experimento. Outros quatro animais adoeceram e foram eutanasiados aos 30, 45, 75 e 100 dias do experimento. O fornecimento de S. carpinifolia foi interrompido em um ovino ao 80° dia do experimento, e o animal foi eutanasiado 70 dias após. Todos os animais foram necropsiados. O consumo variou entre 11 e 30 g/kg/dia da planta seca. As principais alterações clínicas iniciaram a partir do 20° dia com emaciação progressiva e leve diarréia. Os sinais neurológicos iniciaram no 25° dia e eram caracterizados por ataxia com dismetria, tremores da cabeça, posturas atípicas, quedas freqüentes, lentidão dos movimentos, dificuldade em apreender e deglutir os alimentos. Esses sinais clínicos se acentuavam quando os animais eram forçados a se movimentar. O ovino que parou de consumir Sida carpinifolia, recuperou-se clinicamente e 11 dias após a interrupção não apresentava mais alterações clínicas. Na necropsia havia aumento de volume dos linfonodos mesentéricos em cinco dos sete ovinos. Ao exame histológico as alterações mais significativas estavam presentes no sistema nervoso central e constavam de distensão e vacuolização citoplasmáticas afetando principalmente as células de Purkinje do cerebelo, os neurônios do córtex cerebral, do tálamo, do mesencéfalo e dos cornos ventrais da medula espinhal. Também foram observados esferóides axonais mais freqüentes na camada granular do cerebelo. A vacuolização citoplasmática foi observada também no epitélio dos ácinos pancreáticos e dos túbulos renais, nas células foliculares da tireóide, nos hepatócitos e macrófagos de órgãos linfóides. As lesões ultra-estruturais observadas foram vacuolizações citoplasmáticas, algumas envoltas por membranas, em neurônios de Purkinje do cerebelo e nas células foliculares da tireóide. O ovino que permaneceu 70 dias sem consumir S. carpinifolia não apresentou alterações histológicas.

Acute and subacute toxicity of Cochlospermum regium (Mart. & Schr.) pilger.

The toxicity of a hydroethanol extract of the subterranean part of Cochlospermum regium was evaluated in mice and rats. The extract had moderate acute toxicity when administered intraperitoneally and low toxicity upon oral administration. A subacute toxicity test revealed that the extract is well tolerated by these animals.