Crystal Design, Antitumor Activity and Molecular Docking of Novel Palladium(II) and Gold(III) Complexes with a Thiosemicarbazone Ligand.

The current research describes the synthesis and characterization of 2-acetylpyridine N(4)-cyclohexyl-thiosemicarbazone ligand (HL) and their two metal complexes, [Au(L)Cl][AuCl2] (1) and [Pd(L)Cl]·DMF (2). The molecular structures of the compounds were determined by physicochemical and spectroscopic methods. Single crystal X-ray diffraction was employed in the structural elucidation of the new complexes. The complexes showed a square planar geometry to the metal center Au(III) and Pd(II), coordinated with a thiosemicarbazone molecule by the NNS-donor system and a chloride ion. Complex (1) also shows the [AuCl2]- counter-ion in the asymmetric unit, and complex (2) has one DMF solvent molecule. These molecules play a key role in the formation of supramolecular structures due to different interactions. Noncovalent interactions were investigated through the 3D Hirshfeld surface by the dnorm function and the 2D fingerprint plots. The biological activity of the compounds was evaluated in vitro against the human glioma U251 cells. The cytotoxicity results revealed great antitumor activity in complex (1) compared with complex (2) and the free ligand. Molecular docking simulations were used to predict interactions and properties with selected proteins and DNA of the synthesized compounds.

Dithiocarbazate ligands and their Ni(II) complexes with potential biological activity: Structural, antitumor and molecular docking study.

In the search for new metal complexes with antitumor potential, two dithiocarbazate ligands derived from 1,1,1-trifluoro-2,4-pentanedione (H2L1) and (H2L2) and four Ni(II) complexes, [Ni(L1)PPh3] (1), [Ni(L1)Py] (2), [Ni(L2)PPh3] (3), and [Ni(L2)Py] (4), were successfully synthesized and investigated by physical-chemistry and spectroscopic methods. The crystal structure of the H2L1 and the Ni(II) complexes has been elucidated by single-crystal X-ray diffraction. The obtained structure from H2L1 confirms the cyclization reaction and formation of the pyrazoline derivative. The results showed square planar geometry to the metal centers, in which dithiocarbazates coordinated by the ONS donor system and a triphenylphosphine or pyridine molecule complete the coordination sphere. Hirshfeld surface analysis by d norm function was investigated and showed π-π stacking interactions upon the molecular packing of H2L1 and non-classical hydrogen bonds for all compounds. Fingerprint plots showed the main interactions attributed to H⋅H C⋅H, O⋅H, Br⋅H, and F⋅H, with contacts contributing between 1.9% and 38.2%. The mass spectrometry data indicated the presence of molecular ions [M + H]+ and characteristic fragmentations of the compounds, which indicated the same behavior of the compounds in solution and solid state. Molecular docking simulations were studied to evaluate the properties and interactions of the free dithiocarbazates and their Ni(II) complexes with selected proteins and DNA. These results were supported by in vitro cytotoxicity assays against four cancer cell lines, showing that the synthesized metal complexes display promising biological activity.

Comparative investigation of Cu(II) complexes with dithiocarbazate: Structural design, theoretical calculation, and in vitro antitumor activity.

The present work reports the synthesis and investigation by semi-empirical Density Functional Theory (DFT), physical chemistry, and spectroscopic methods of two dithiocarbazates, 2-acetylpyridine-S-p-bromobenzyl-dithiocarbazate (HL1) and 2-acetylpyridine-S-p-nitrobenzyl-dithiocarbazate (HL2) and their Cu(II) complexes, [Cu(L1)Cl] (1), [Cu(L1)Br] (2), [Cu(L2)Cl] (3) and [Cu(L2)Br] (4). Single crystal X-ray analyzes showed distorted square planar geometry to the metal centers, which tridentate ligands coordinated by the NNS system and an additional halogen (Cl- or Br-) to complete the coordination sphere. Mass spectrometry data indicated the presence of [Cu(L1)(DMF)]+ and [Cu(L2)(DMF)]+, due to the exchanging of chloride/bromide ions and characteristic fragmentations of the compounds. The DFT composite method B97-3c was employed to optimize the geometries of ligands and complexes and IR spectra were calculated revealing good agreement with experimental data. Hydrogen bonds and π⋅⋅⋅π stacking interactions upon the molecular packing were investigated by Hirshfeld surface and fingerprint plots with the main interactions attributed to the H⋅⋅⋅H contacts. The biological activity of the dithiocarbazates and their Cu(II) complexes were evaluated in vitro against the human glioma U251 cells. Results revealed that the free dithiocarbazates present great in vitro antitumor activity that is increased after the complexation with copper. The measurement of cytotoxicity of the compounds showed biological activity in a low range of concentration, which indicates high efficiency as potential drugs.

Structural, theoretical and biological activity of mono and binuclear nickel(II) complexes with symmetrical and asymmetrical 4,6-diacetylresorcinol-dithiocarbazate ligands.

The present work reports the synthesis and a structural study of two novel dithiocarbazate, the 4,6-diacetylresorcinol-S-benzyldithiocarbazate (H3L1) and the 4,6-diacetylresorcinol-bis(S-benzyldithiocarbazate) (H4L2), and their Ni(II) complexes, [Ni(HL1)(Py)] (1) and [Ni2(L2)(PPh3)2] (2). Single crystal X-ray analyzes reveal mono and binuclear complexes and the metal centers with distorted square planar geometry. The analyses of the Hirshfeld surface and fingerprints plots revealed intermolecular contacts attributed to the H···H and C···H/H···C bonds. The Density Functional Theory (DFT), with the B3LYP functional and 6-311-G(d,p)/LanL2DZ basis sets, was employed to optimize the geometries of synthesized compounds. From the resulting geometries, the highest occupied and lowest unoccupied molecular orbital maps (HOMO-LUMO), orbital energy gap, electron localization function (ELF), electron density, natural bond orbital (NBO) analysis, and complexation of the ligands with Ni(II) were calculated supporting the experimental data. The ESI (+)-MS/MS data indicated the presence in solution of the characteristic fragmentation with the [H3L1]+ and [H4L2]+ molecular ions for the ligands. The pharmacological potential of the dithiocarbazate ligands and their Ni(II) complexes were evaluated in vitro against MDA-MB-231 human breast cancer cells. A remarkable cytotoxic activity was observed, more evident for free ligands than complexes at low concentrations; however, this latter showed a better dose-response pattern, being more attractive in terms of pharmacokinetics and therapeutic window.

Clinical Relevance of Alternative Lengthening of Telomeres in Cancer.

The alternative lengthening of telomere (ALT) is a pathway responsible for cell immortalization in some kinds of tumors. Since the first description of ALT is relatively recent in the oncology field, its mechanism remains elusive, but recent works address ALT-related proteins or cellular structures as potential druggable targets for more specific and efficient antitumor therapies. Moreover, some new generation compounds for antitelomerase therapy in cancer were able to provoke acquisition of ALT phenotype in treated tumors, enhancing the importance of studies on this alternative lengthening of the telomere. However, ALT has been implicated in different - sometimes opposite - outcomes, according to the tumor type studied. Then, in order to design and develop new drugs for ALT+ cancer in an effective way, it is crucial to understand its clinical implications. In this review, we gathered works published in the last two decades to highlight the clinical relevance of ALT on oncology.

Specific Cytostatic and Cytotoxic Effect of Dihydrochelerythrine in Glioblastoma Cells: Role of NF-κB/ß-catenin and STAT3/IL-6 Pathways.

BACKGROUND: A glioblastoma is a primary CNS tumor that is more aggressive and lethal than other brain tumors. Its location, rapid proliferation, invasive growth, angiogenesis and immunosuppression are the main factors that limit its treatment, making it a major challenge to neuro-oncology. OBJECTIVE: This study investigated the in vitro effects of the alkaloid dihydrochelerythrine (DHC), which is extracted from Zanthoxylum stelligerum, on the viability, proliferation, cell death and ß-catenin, NFκB, STAT3/pSTAT3 and interleukins roles. METHOD: In vitro experimental models of human (U251 and GL-15) and murine (C6) glioblastoma cells were cultured in the presence of DHC at increasing concentrations for MTT assay and exclusion trypan blue dye to determine EC50. Afterward, C6 and U251 cells were treated with 100 µM DHC or DMSO 0.1% for cell cycle, annexin and expression of ß-catenin/NFκB/STAT3/pSTAT3 by flow cytometry or immunofluorescence. Interleukin quantification was made by Cytometric Bead Array. RESULTS: A significant decrease was observed in C6 and U251 cell viability in a time and dose-dependent manner. GL-15 cell viability decreased only when treated with 200 µM DHC. This maximum concentration affected neither astrocytes nor microglia viability. A cytostatic effect of DHC was observed in C6 and U251 cells after 48 h of 100 µM DHC treatment. After 72 h of DHC treatment, C6 presented 80% of annexin-V+ cells compared to 10% of annexin-V+ U251 cells. C6 cells demonstrated significant high levels of NFκ B and ß-catenin cytoplasmic fraction. Additionally, DHC treatment resulted in higher significant levels of IL-6 than did other interleukins and STAT3 up-regulation in U251 cells. CONCLUSION: These results demonstrate that DHC acts as a chemosensitizing agent selective for glioma cells not affecting non-tumor cells. Considering tumor heterogeneity, DHC demonstrated an anti-cancer potential to activate different cell death pathways. DHC demonstrated could be used for chemotherapy and immunotherapy applications in glioblastomas in the future.

Long-term exposure to MST-312 leads to telomerase reverse transcriptase overexpression in MCF-7 breast cancer cells.

Telomerase is an enzyme responsible for telomere maintenance in almost all human cancer cells, but generally not expressed in somatic ones. Therefore, antitelomerase therapy is a potentially revolutionary therapeutic strategy, and the antitumor activity of telomerase inhibitors (TI) has been studied extensively recently, mainly for breast cancer. However, the effects expected from treatment with TI will appear only after many cell divisions, but the effects of this long-term approach are unknown. In this work, the consequences of 3120 h exposure of human breast cancer cells to TI MST-312 were investigated. MCF-7 cells were treated with MST-312 at a subtoxic concentration for a long time, and then cell morphology, viability, senescence, and proliferation were analyzed by phase-contrast microscopy, MTT assay, ß-galactosidase test, and the trypan blue exclusion assay, respectively. Also, chromosomal stability was evaluated by classical cytogenetic analysis. The average length of telomeres and telomerase reverse transcriptase expression were accessed by real-time PCR and real-time RT-PCR, respectively. The MST-312 showed cytotoxic action and promoted telomere erosion, senescence, and chromosome aberrations, as expected, but in a small proportion. Nevertheless, the proliferation rate of the culture was not affected. As the main effect, the chronic exposure led to cell adaptation by overexpression of telomerase in response to the inhibitor, which is a potential cause of therapeutic failure and may be associated with a poor prognosis. In conclusion, despite the high therapeutic potential of TIs such as MST-312, the molecular outcomes of long-term exposure of tumors on these drugs have to be evaluated when considering their clinical application, especially for breast cancer treatment.

Tumores de cães e gatos diagnosticados no semiárido da Paraíba / Tumors in dogs and cats diagnosed in semiarid of Paraíba, Brazil

Objetivou-se com este estudo determinar a frequência dos tumores diagnosticados em cães e gatos no Hospital Veterinário da Universidade Federal de Campina Grande (UFCG), Patos, Paraíba, Brasil, entre os anos de 2003 a 2010. Foram revisados todos os protocolos de necropsias e biópsias realizadas no Laboratório de Patologia Animal da referida instituição, e computados os dados referentes aos animais afetados. Os tumores mais frequentes em cães ocorreram na pele e anexos (46,7%), seguido da glândula mamária (24%), sistema genital (10,3%) e sistema digestório (6,5%). Os tumores malignos foram mais frequentes que os benignos (p=0,001), representando 78% e 22% respectivamente. Em gatos, as frequências de neoplasmas de pele e glândula mamária foram idênticas (39,4% cada), seguidas das do sistema digestório (8,5%) e fígado (5,7%). Os tumores malignos representaram 95,8% dos tumores diagnosticados nesta espécie. Cães sem raça definida tiveram menor frequência (16%) de tumores do que animais de diferentes raças (37,2%) (p<0,0001). A ampla variedade de neoplasmas que acomete cães e gatos dificulta ao veterinário o diagnóstico clínico e o tratamento das mesmas, sendo recomendável o diagnóstico histológico sistemático de todas as lesões suspeitas de serem neoplasias. Além disso, são necessários estudos que determinem os fatores epidemiológicos envolvidos no desenvolvimento dos tumores que acometem os cães e gatos, nas diferentes regiões, a fim de serem tomadas medidas para diminuir sua ocorrência e letalidade.

This paper reports the frequency of tumors diagnosed in dogs and cats at the Veterinary Hospital of the Federal University of Campina Grande in Patos, northeastern Brazil, between 2003 and 2010. All necropsy and biopsy protocols from the Pathology Laboratory were revised and data related to the tumors were analyzed. In dogs, tumors of the skin and anexa were the most frequently diagnosed (46.7%), followed by tumors of the mammary gland (24%), genital system (10,3%), and alimentary system (6.5%). Malignant tumors (78%) were more frequent than bening tumors (22%) (p=0.001). In cats the frequency of skin and mammary gland tumors was the same (39.4%), followed by tumors of the digestive system (8.5%) and liver (5.7%). In cats, 95.8% of the tumors were malignant. Due to the diversity of the tumors observed in dogs and cats it is difficult for the practitioner to diagnose and treat tumors in these species. As a result, the systematic histologic diagnosis and the determination of the epidemiology of the tumors, in the different regions, are necessary to decrease tumor mortality.

Oxidative stress in neurodegenerative diseases: mechanisms and therapeutic perspectives.

The incidence and prevalence of neurodegenerative diseases (ND) increase with life expectancy. This paper reviews the role of oxidative stress (OS) in ND and pharmacological attempts to fight against reactive oxygen species (ROS)-induced neurodegeneration. Several mechanisms involved in ROS generation in neurodegeneration have been proposed. Recent articles about molecular pathways involved in ROS generation were reviewed. The progress in the development of neuroprotective therapies has been hampered because it is difficult to define targets for treatment and determine what should be considered as neuroprotective. Therefore, the attention was focused on researches about pharmacological targets that could protect neurons against OS. Since it is necessary to look for genes as the ultimate controllers of all biological processes, this paper also tried to identify gerontogenes involved in OS and neurodegeneration. Since neurons depend on glial cells to survive, recent articles about the functioning of these cells in aging and ND were also reviewed. Finally, clinical trials testing potential neuroprotective agents were critically reviewed. Although several potential drugs have been screened in in vitro and in vivo models of ND, these results were not translated in benefit of patients, and disappointing results were obtained in the majority of clinical trials.

Bovine cryptococcal meningoencephalitis.

Cryptococcal meningitis and encephalitis is reported in a 5-year-old bull. The clinical signs included multifocal neurological deficits manifested by hypermetria, ataxia, depression, circling, impaired vision, head pressing, low head carriage, wide-based stance, and falling to the side or backwards. At necropsy, 6 cavities with a gelatinous content were observed in the brain and brain stem, and the meninges were thickened and off white. Numerous yeasts, with a nonstaining capsule, and associated mild inflammatory reaction were observed histologically. Specimens for culture were not collected at necropsy, but the identity of the yeast in tissue sections as Cryptococcus neoformans var. grubii was supported by immunohistochemistry.

Intoxicação por Portulaca elatior (Portulacaceae) em caprinos / Poisoning by Portulaca elatior (Portulacaceae) in goats

Um surto de intoxicação espontânea por Portulaca elatior foi diagnosticado no município de Aroeiras, Paraíba, na época das chuvas. Entre os meses de fevereiro e abril, em um rebanho de 316 caprinos, 16 adoeceram, sendo 15 de um lote de 16 caprinos que tinham sido introduzidos recentemente na fazenda e um animal do rebanho já existente na fazenda. Os caprinos apresentaram intensa salivação, relutância em se movimentar, tremores de lábios, marcha incoordenada, diarreia, timpanismo, dor abdominal, gemidos, desidratação e berros constantes. A evolução da enfermidade variou de 2 a 48 horas; 13 caprinos morreram e três se recuperaram. As lesões macroscópicas caracterizavam-se por mucosa ruminal e do retículo avermelhadas, serosa do rúmen hemorrágica, mucosa abomasal avermelhada com áreas ulceradas e mucosa do intestino delgado com equimoses. No exame histopatológico observou-se degeneração e necrose das células epiteliais dos pré-estômagos com formação de vesículas e infiltrado inflamatório neutrofílico. Suspeita de ter causado o surto, Portulaca elatior foi administrada a três caprinos nas doses de 40, 20 e 10 gramas de planta fresca por kg de peso animal (g/kg). Esses caprinos apresentaram sinais semelhantes aos casos espontâneos. Os animais que ingeriram 20 e 40g/kg morreram e o que ingeriu 10g/kg se recuperou. Microscopicamente foram observadas lesões do sistema digestivo semelhantes às dos casos espontâneos. A reprodução experimental da intoxicação, com sinais clínicos e lesões histológicas semelhantes às dos casos espontâneos, comprova que a doença foi causada por Portulaca elatior. P. elatior apresentou níveis de oxalatos de 6,37 por cento e outra planta, identificada como Blutaparon vermiculare e que ocorria em grande quantidade nas pastagens, apresentou níveis de oxalatos de 5,29 por cento. B. vermiculare foi administrada experimentalmente a um caprino na dose de 40g/kg, sem que o animal apresentasse sinais clínicos[...]

An outbreak of poisoning by Portulaca elatior was diagnosed in the state of Paraíba, northeastern Brazil, during the rainy season. Between February and April, 16 out of 316 goats were affected and 13 died. Fifteen of the affected animals were from a flock of 16 goats introduced on the farm at the beginning of the rainy season. Clinical signs were intense salivation, reluctance to move, lip tremors, slight uncoordinated gait, diarrhea, bloat, abdominal pain, groans, dehydration and constant bellowing. The course of the disease ranged from 2 to 48 hours; 13 goats died and three recovered. Gross lesions were reddening of the mucosa of rumen and reticulum, hemorrhages in the ruminal serosa, ulcerations of the abomasal mucosa, and ecchymoses in the small intestinal mucosa. Histological examination revealed degeneration and necrosis of epithelial cells with vesicle formation in the fore stomachs associated with infiltration by neutrophils. Suspected to have caused the outbreak, Portulaca elatior was administered experimentally to three animals at doses of 40, 20 and 10 grams of the fresh plant per kg bodyweight, respectively. The goats that ingested 20 and 40g/kg died, and the one that ingested 10g/kg showed clinical signs but recovered. These animals showed similar clinical signs and histological lesions as those seen in the goats poisoned spontaneously, demonstrating that the disease was caused by the ingestion of Portulaca elatior. Oxalate concentration were determined in P. elatior and in another plant identified as Blutaparon vermiculare. P. elatior contained 6.37 percent of total oxalates and B. vermiculare 5.29 percent. B. vermiculare was administered experimentally to one goat at a dose of 40g/kg, without causing clinical signs. These results and the absence of oxalate crystals in the digestive system and kidneys of the goats necropsied suggest that poisoning by P. elatior is not caused by high oxalate concentration in the plant.

Focal symmetrical encephalomalacia in a goat.

Focal symmetrical encephalomalacia (FSE) is the most prominent lesion seen in the chronic form of enterotoxemia caused by Clostridium perfringens type D in sheep. However, this lesion has not been reported in goats. The current paper reports a case of FSE in a goat from the state of Paraíba in the Brazilian semiarid region. As reported by the farmer, 30, 4-48-month-old animals from a flock of 150 goats died after showing nervous signs, including blindness and recumbence, for periods varying between 1 and 14 days. The flock was grazing native pasture supplemented with wheat and corn bran. Additionally, lactating goats were supplemented with soybeans. A 4-month-old goat with nervous signs was examined clinically and then necropsied 3 days after the onset of clinical signs. Bilateral, focal, and symmetrical areas of brown discoloration were observed in the internal capsule and thalamus. Histologic lesions in these areas consisted of multifocal, bilateral malacia with a few neutrophils; endothelial cell swelling; perivascular edema; and hemorrhages. The etiology of these lesions was not determined. However, FSE is considered pathognomonic for C. perfringens type D enterotoxemia in sheep, and it is speculated that this microorganism was the etiologic agent in the present case. The flock had been vaccinated against type D enterotoxemia only once, approximately 3 months before the beginning of the outbreak. Insufficient immunity due to the incorrect vaccination protocol, low efficacy of the vaccine used, and a diet including large amounts of highly fermentable carbohydrates were suspected to be predisposing factors for this outbreak.

Focal symmetrical encephalomalacia in sheep / Encefalomalacia focal simétrica em ovino

Focal symmetrical encephalomalacia (FSE) is the most prominent lesion seen in the chronic form of enterotoxemia by Clostridium perfringens type D. This paper reports FSE in sheep in Brazil. Six deaths occurred within a seven days period in a flock of 70, four to 30-month-old Santa Inês sheep in the state of Paraíba in the Brazilian semiarid. The flock was grazing a paddock of irrigated sprouting Cynodon dactylon (Tifton grass), and supplemented, ad libitum, with a concentrate of soybean, corn and wheat. Nervous signs included blindness and recumbence. A 19 month-old sheep was examined clinically and necropsied after a clinical course of three days. Gross lesions were herniation of the cerebellar vermis and multifocal, bilateral, symmetric brownish areas in the internal capsule, thalamus and cerebellar peduncles. Histologic lesions were multifocal, bilateral malacia with some neutrophils, swelling of blood vessels endothelium, perivascular edema, and hemorrhages. The flock was vaccinated, before the outbreak, with only one dose of Clostridium perfringens type D vaccine. Two factors are suggested to be important for the occurrence of the disease: insufficient immunity due to the incorrect vaccination; and high nutritional levels by the supplementation with highly fermentable carbohydrates.

Encefalomalacia focal simétrica (EFS) é a lesão mais proeminente vista nas formas subaguda ou crônica da enterotoxemia por Clostridium perfringens tipo D. Este trabalho relata EFS em ovinos no semiárido do estado da Paraíba. Seis ovinos morreram, em um período de sete dias, dentro de um rebanho de 70 animais, da raça Santa Inês, entre 4-30 meses de idade, que pastavam em piquete de Cynodon dactylon (capim Tifton), que estava rebrotando. Os ovinos eram suplementados com um concentrado de soja, trigo e milho. Os sinais nervosos incluíam cegueira e decúbito lateral. Um ovino de 19 meses de idade foi examinado clinicamente e necropsiado, depois de um curso clínico de 3 dias. Macroscopicamente foram observadas herniação do cerebelo e áreas acastanhadas, multifocais, simétricas e bilaterais na cápsula interna, tálamo e pedúnculo cerebelar. Histologicamente observou-se malacia, bilateral e simétrica, com alguns neutrófilos, tumefação das células endoteliais dos vasos sanguíneos, edema perivascular e hemorragia. O rebanho foi vacinado, antes do surto, com umaúnica dose de vacina para Clostridium perfringens tipo D. Dois fatores são sugestivos quanto a importância da ocorrência da enfermidade: imunidade insuficiente devida à vacinação incorreta; e altos níveis nutricionais da suplementação com carboidratos altamente fermentáveis.

Poisoning of goats by the pods of Luetzelburgia auriculata.

Farmers report that the pods of Luetzelburgia auriculata cause digestive signs and death when ingested by goats. To demonstrate the toxicity of the pods of this plant 12 goats were divided into 4 groups of 3 goats each. Groups 1, 2, 3 and 4 were administered 2.5, 1, 0.5 and nil g of pods per kg body weight, respectively. Goats in Groups 1 and 2 developed decreased ruminal movements followed by anorexia, depression and soft feces or diarrhea. Goats in Group 1 died 59-106 h after first showing clinical signs. Goats in Group 2 also regurgitated rumen content, but all recovered 65-90 h after first showing clinical signs. The only clinical sign shown by goats in Group 3 was regurgitation of rumen content, and all goats recovered 5.5-24 h after first regurgitating. All goats in Group 4 remained normal. The goats that died were necropsied and found to have a reddish mucosa of the forestomachs that detached easily from the underlying tissues. Other lesions included diffuse reddening of the mucosa of the abomasum and intestine. Histological examination of the mucosa of the forestomachs showed diffuse ballooning degeneration of keratinocytes, with necrosis and vesicle and pustule formation in the epithelium. In some areas there was sloughing of the ruminal epithelium. These results demonstrate that the pods of L. auriculata are toxic and responsible for field outbreaks of poisoning in goats in the state of Piaui.

Plantas tóxicas para ruminantes e eqüídeos no Norte Piauiense / Toxic plants for ruminants and equidae in Northern Piauí

Este trabalho teve por objetivo realizar um levantamento sobre as plantas tóxicas para ruminantes e equídeos na Mesorregião Norte do Piauí. Foram feitas 71 entrevistas a médicos veterinários, engenheiros agrônomos, técnicos agrícolas e produtores de 16 municípios, entrevistando pelo menos quatro pessoas por município. As plantas comprovadamente tóxicas que foram apontadas com maior frequência na região estudada foram Ipomoea asarifolia, que causa intoxicações em pequenos ruminantes em todas as áreas visitadas. Stryphnodendron coriaceum pelas mortes que ocasiona é, aparentemente, a planta que causa maiores perdas econômicas na mesorregião estudada. Enterolobium contortisiliquum também foi citada como causa importante de sinais digestivos, abortamentos e fotossensibilização em bovinos da região. Os entrevistados confirmaram a ocorrência de surtos de intoxicação em bovinos por Thiloa glaucocarpa no inicio do período chuvoso. Manihot spp. e Piptadenia macrocarpa são plantas cianogênicas apontadas como causa de mortes superagudas em bovinos. Outras plantas relatadas como tóxicas pelos entrevistados, mas sem que haja comprovação de sua toxicidade, foram Buchenavia tomentosa, Caesalpinia sp., Brunfelsia sp., Luetzelburgia sp., Hybantus ipecaconha, Phisalys angulata e Spondias luta. De acordo com os entrevistados os frutos de Buchenavia tomentosa causam sinais digestivos e abortos em caprinos, ovinos e bovinos. Produtores relatam surtos de intoxicação em caprinos que apresentam sinais digestivos e morte após a ingestão de favas de Luetzelburgia sp. Brunfelsia sp. é relatada como causa de alterações nervosas, no começo das chuvas, quando os animais ingerem as folhas e flores e os asininos são aparentemente mais afetados. Os frutos de Spondias luta foram mencionados como causa de diarréia em caprinos. Experimentos não publicados demonstraram a toxicidade de Brunfelsia sp. em ovinos e de Luetzelburgia sp. como causa de sinais digestivos e mortes ...

The objective of this study was to survey toxic plants for ruminants and equidae in northern Piauí. Seventy one persons were interviewed, including farmers, veterinary practitioners, agronomists, and agrarian technicians from 16 municipalities, performing at least four interviews in each municipality. The most common plant mentioned as a cause of poisoning was Ipomoea asarifolia, which is a well known cause of tremogenic disease in ruminants. Stryphnodendron coriaceum which causes digestive signs was referred as a common cause of death, and is probably the plant that causes most cattle deaths in the region. Enterolobium contortisiliquum was also mentioned as a frequent cause of digestive signs, abortion and photosensitization in cattle. Outbreaks of nephrosis caused by Thiloa glaucocarpa are frequent at the beginning of the raining season. Poisoning by the cyanogenic plants Manihot spp. e Piptadenia macrocarpa are a cause of peracute deaths. Other plants mentioned as toxic were Buchenavia tomentosa, Caesalpinia sp., Brunfelsia sp., Luetzelburgia sp., Hybantus ipecaconha, Phisalys angulata, and Spondias luta. Farmers report that goats are poisoned by the ingestion of the pods of Luetzelburgia sp., which causes digestive signs and death. The ingestion of the fruits of Buchenavia tomentosa is associated with digestive signs and and abortion in ruminants. Brunfelsia sp. is mentioned as a cause of nervous signs at the start of the raining season and donkeys are apparently more affected. The consumption of the fruits of Spondias luta are associated with diarrhea in goats. Recent unpublished experiments demonstrated the toxicity of Brunfelsia sp. as a cause of nervous signs and of Luetzelburgia sp. as a cause of digestive signs in goats. Experiments with other plants are necessary to confirm their toxicity.

Intoxicações por plantas diagnosticadas em ruminantes e equinos e estimativa das perdas econômicas na Paraíba / Plant poisonings diagnosed in ruminants and horses and estimation of the economical losses in Paraíba

Foi realizado um levantamento dos surtos de intoxicações por plantas em ruminantes e equinos diagnosticados no Laboratório de Patologia Veterinária (LPV), do Hospital Veterinário da Universidade Federal de Campina Grande, Campus de Patos, Paraíba, no período de 2000-2007. Em bovinos 7,4 por cento dos diagnósticos realizados pelo LPV foram intoxicações por plantas. Foram diagnosticadas intoxicações por Centhraterum brachylepis (um surto), Brachiaria spp. (um surto), Crotalaria retusa (dois surtos), Ipomoea batatas (um surto), Marsdenia sp. (um surto), gramíneas contendo nitratos e nitritos (um surto por Echinochloa polystachya e dois surtos por Pennisetum purpureum), Palicourea aeneofusca (um surto), Prosopis juliflora (três surtos), Nerium oleander (um surto) e Mimosa tenuiflora (sete surtos). Na espécie ovina 13 por cento dos diagnósticos foram intoxicações por plantas. Os surtos foram causados por Ipomoea asarifolia (quatro surtos), Brachiaria spp. (três surtos), Crotalaria retusa (dois surtos), Tephrosia cinerea (dois surtos), Panicum dichotomiflorum (um surto), Mascagnia rigida (um surto) e malformações associadas à ingestão de Mimosa tenuiflora (20 surtos). Nos caprinos, 6,4 por cento dos diagnósticos corresponderam à intoxicação por plantas. Sete surtos foram causados por Mimosa tenuiflora, um por Ipomoea asarifolia, um por Ipomoea carnea, um por Ipomoea riedelli, três por Prosopis juliflora, um por Arrabidaea corallina, dois por Aspidosperma pyrifolium, dois por Turbina cordata e um por Opuntia ficus-indica. Na espécie equina 14 por cento das doenças diagnosticadas foram devidas a intoxicações por plantas, sendo 12 surtos por Crotalaria retusa e um por Turbina cordata. As perdas na Paraíba por plantas tóxicas são estimadas em 3.895 bovinos, 8.374 ovinos, 6.390 caprinos e 366 equinos, que representam uma perda econômica anual, por morte de animais, de R$ 2.733.097,00. São relatados alguns aspectos epidemiológicos, sinais clínicos...

ABSTRACT This paper reports plant poisonings in ruminants and horses, diagnosed between 2000 and 2007, in the Veterinary Pathology Laboratory at the Federal University of Campina Grande, in the city of Patos, state of Paraíba. In cattle, 7.4 percent of the diseases diagnosed were caused by poisonous plants. Outbreaks were caused by Centhraterum brachylepis (1), Brachiaria spp. (1), Crotalaria retusa (2), Ipomoea batatas (1), Marsdenia sp. (1), grass containing nitrites (3 outbreaks, 1 by Echinochloa polystachya and 2 by Pennisetum purpureum), Palicourea aeneofusca (1), Prosopis juliflora (3), Nerium oleander (1), and Mimosa tenuiflora (7). In sheep, 13 percent of the diseases diagnosed were caused by toxic plants. Four outbreaks were caused by Ipomoea asarifolia, 3 by Brachiaria spp., 2 by Crotalaria retusa, 2 by Tephrosia cinerea, 1 by Panicum dichotomiflorum, 1 by Mascagnia rigida, and 20 by Mimosa tenuiflora. In goats, 6.4 percent of the diseases were caused by toxic plants. Seven outbreaks were caused by Mimosa tenuiflora, 1 by Ipomoea asarifolia, 1 by Ipomoea carnea, 1 by Ipomoea riedelli, 3 by Prosopis juliflora, 1 by Arrabidaea corallina, 2 by Aspidosperma pyrifolium, and 2 by Turbina cordata. In horses, 14 percent of the diagnosed diseases were due to plants poisonings including 12 outbreaks caused by Crotalaria retusa and one by Turbina cordata. Annual losses in the state of Paraíba by deaths of livestock are estimated in 3,895 cattle, 8,374 sheep, 6,390 goats, and 366 horses, which represent about US$ 1,380,000. Epidemiologic, clinical and pathologic aspects of poisonings by Crotalaria retusa in cattle, Brachiaria spp. in sheep, Prosopis juliflora in cattle and goats, Nerium oleander in cattle, Opuntia ficus-indica in goats, and Turbina cordata in horses and goats are reported.

Paratuberculose em caprinos e ovinos no Brasil / Paratuberculosis in goats and sheep in Brazil

Este trabalho relata, pela primeira vez no Brasil, no Estado da Paraíba, paratuberculose em dois rebanhos com criação conjunta de caprinos e ovinos. Na Fazenda 1, de um rebanho de 33 caprinos e 13 ovinos, uma cabra adulta apresentou emagrecimento progressivo por aproximadamente um ano e fezes pastosas um mês antes da morte. Todos os animais do rebanho foram tuberculinizados com a prova comparativa. Um ovino (2,2 por cento) teve resultado positivo à tuberculina aviar e em dois o teste foi inconclusivo. Na Fazenda 2, com 200 ovinos e 80 caprinos, foi afetada uma ovelha adulta que apresentou emagrecimento progressivo por aproximadamente um ano e fezes pastosas por aproximadamente 20 dias. Todos os ovinos com mais de 4 meses de idade e 23 caprinos foram tuberculinizados com tuberculina aviar; em 47 (25,4 por cento) o resultado foi positivo, em 115 (61,5 por cento) inconclusivo e em 25 (13,4 por cento) negativo. Entre as cabras não houve nenhuma positiva à tuberculina aviar, mas em 11 (47,8 por cento) o teste foi inconclusivo e em 12 (52,2 por cento) foi negativo. Na necropsia dos dois animais com sinais clínicos os linfonodos mesentéricos estavam aumentados de tamanho e edemaciados. O ovino afetado da Fazenda 2, apresentou espessamento e enrugamento da mucosa do intestino, principalmente no íleo e válvula íleo-cecal. Microscopicamente o caprino e o ovino com sinais clínicos apresentaram lesões semelhantes, caracterizadas por granulomas com predominância de macrófagos espumosos, na lâmina própria e submucosa do intestino e linfonodos mesentéricos. O ovino positivo à tuberculina e um caprino negativo na Fazenda 1 foram eutanasiados e apresentaram discreto espessamento da mucosa do íleo. Na histologia foi observado infiltrado preferentemente linfocítico. Em todos os casos dentro de macrófagos e linfócitos havia bacilos ácool-ácidos resistentes, positivos na imunohistoquímica para Mycobacterium spp. Sugere-se a necessidade de estudar a prevalência ...

This paper reports paratuberculosis in sheep and goats for the first time in Brazil. On Farm 1 in a flock of 33 goats and 13 sheep, one adult female goat presented progressive weight loss during about one year, and soft feces during one month before death. All the animals from the flock were submitted to the comparative tuberculin test. One sheep was positive to the avian tuberculin (2.2 percent) and in two the results were inconclusive. On Farm 2, in a flock of 200 sheep and 80 goats, one adult ewe presented progressive weight loss during about one year, and soft feces during 20 days before death. All sheep older than four months of age and 23 goats were submitted to tuberculin test with avian tuberculin; 47 (25.4 percent) sheep were positive, 115 (61.5 percent) had inconclusive results, and 25 (13.4 percent) were negative. No positive tuberculin test were observed in the goats, but in 11 (47.8 percent) the test was inconclusive and in 12 (52.2 percent) was negative. At necropsy both affected animals had enlarged mesenteric lymph nodes. In the affected sheep, the gut wall was thickened and corrugated, mainly in the ileum and ileocecal valve. Histologically, granulomas with mainly foamy macrophages were observed in the lamina propria and submucosa of the gut, in mesenteric lymph nodes, and in the goat also in the liver. One tuberculin positive sheep and one tuberculin negative goat from Farm 1 were euthanized and necropsied. A mild thickened of the intestinal wall was observed grossly in both animals. Inflammatory infiltrate with mainly lymphocytes was observed on the submucosa and lamina propria of the gut. In the four cases acid-alcohol positive rods, positive for Mycobacterium spp. on immunohistochemical examination were observed in macrophages and lymphocytes. New studies are necessary to know the prevalence and economical impact of paratuberculosis in goats and sheep in Brazil, to determine control measures, and to evaluate the risk ...

Doenças do sistema nervoso central de equídeos no semi-árido / Diseases of the central nervous system in equidae in the Brazilian semiarid

As doenças do sistema nervoso central (SNC) de equídeos representam uma parcela importante das enfermidades diagnosticadas nestas espécies. O estudo destas e de outras enfermidades nas diferentes regiões do país é necessária para estabelecer formas eficientes de controle e profilaxia. O presente trabalho teve como objetivo descrever as características clínicas, epidemiológicas e patológicas das doenças do SNC de equídeos diagnosticadas no Laboratório de Patologia da Universidade Federal de Campina Grande, em Patos, Paraíba, que ocorreram entre janeiro de 2007 e dezembro de 2008. No período estudado, 159 casos ou surtos de doenças de equídeos foram diagnosticados. Destes, 49 (30,8 por cento) afetaram o SNC. A encefalopatia hepática na intoxicação por Crotalaria retusa foi a principal enfermidade com 14 casos (28,5 por cento), seguida por tétano com 13 (26,5 por cento) casos e raiva com 11 (22,,4 por cento) casos. Sete (14,2 por cento) casos foram de traumatismos afetando o SNC. Foram, também, diagnosticados 1 caso de leucoencefalomalacia, 1 de encefalite por herpesvírus eqüino-1, 1 de injeção acidental na artéria carótida, 1 surto de encefalomielite viral equina tipo leste, 1 surto de intoxicação por Turbina cordata e 1 surto de doença tremogênica de causa desconhecida. Cinco casos tiveram diagnóstico inconclusivo. Este trabalho comprova a importância do funcionamento de laboratórios de diagnóstico, nas diferentes regiões do país, para o conhecimento das doenças do rebanho e para a vigilância epidemiológica das mesmas.

Diseases of the central nervous system (CNS) in equidae are important in these species, and their knowledge in the different Brazilian regions is necessary to determine efficient control and preventive measures. This paper reports epidemiologic aspects, clinical signs and pathology of diseases of the CNS in equidae diagnosed by the Veterinary Pathology Laboratory at the Federal University of Campina Grande in the city of Patos, state of Paraíba, northeastern Brazil, during 2002-2008. During the period, 159 cases or outbreaks of those diseases were studied, 49 (30.8 percent) affecting the CNS. Hepatic encephalopathy caused by Crotalaria retusa poisoning, with 14 cases (28.5 percent), was the main disease observed. Tetanus was diagnosed in 13 (26.5 percent) cases and rabies in 11 (22.4 percent). In seven (14.2 percent) cases the death or euthanasia was due to traumatic lesions of the CNS. Also were diagnosed 1 case of leucoencephalomalacia, 1 case of encephalitis by equine herpesvirus-1, 1 case of intracarotid artery injection, 1 outbreak of Eastern equine encephalitis, 1 of Turbina cordata poisoning, and 1 of a tremogenic disease of unknown cause. In 5 cases the diagnosis was inconclusive. This paper indicates the importance of diagnostic veterinary laboratories, in the different Brazilian regions, for the knowledge of livestock diseases.

Intoxicação por Mascagnia rigida (Malpighiaceae) em ovinos e caprinos / Poisoning by Mascagnia rigida (Malpighiaceae) in sheep and goats

Mascagnia rigida é a planta tóxica mais importante para bovinos na região Nordeste, causando morte súbita associada ao exercício. O presente trabalho teve como objetivos descrever três surtos de intoxicação por M. rigida em ovinos e um surto em caprinos no semi-árido da Paraíba, reproduzir experimentalmente a intoxicação em ovinos e caprinos, e comprovar a passagem do princípio ativo de M. rigida pelo colostro destes pequenos ruminantes. Os surtos ocorreram no início do período chuvoso, quando a planta brota antes do que outras forrageiras ou após o final desse período, quando após secarem algumas forrageiras, M. rigida permanece verde. Na reprodução experimental da intoxicação por M. rigida, doses de 10 e 20g/kg de peso animal, com as planta proveniente de duas regiões diferentes, foram letais para três caprinos e três ovinos. Um caprino que ingeriu 20g/kg da planta um ovino que ingeriu 10g/kg, se recuperaram. Dois ovinos e dois caprinos que ingeriram 5g/kg tiveram sinais discretos e se recuperaram. Tanto os casos experimentais quanto os espontâneos apresentaram ingurgitamento das veias jugulares, relutância em caminhar, decúbito externo abdominal, incoordenação, respiração ofegante, depressão, instabilidade e tremores musculares. A morte ocorreu após um curso clínico de alguns minutos a 27h40 min. As principais lesões foram edema pulmonar e vacuolização e necrose de células epiteliais dos túbulos renais. Para testar se o princípio ativo de M. rigida é eliminado pelo leite causando morte súbita nas crias foi realizado um experimento com duas cabras e cinco ovelhas que ingeriram, diariamente, 2g/kg de M. rigida, nos 15 dias anteriores ao parto. Uma ovelha que tinha gestação gemelar abortou depois de ter ingerido a planta por 10 dias. Os cordeiros das demais ovelhas mamaram normalmente o colostro sem aprestar sinais clínicos. O cabrito de uma cabra mamou o colostro e 5 minutos após morreu subitamente...(AU)

Mascagnia rigida is the most important toxic plant for cattle in the Northeastern region of Brazil, causing sudden death during exercise. The objectives of this research were to report three outbreaks of poisoning by M. rigida in sheep and one in goats in the semiarid of the state of Paraíba, to reproduce experimentally the disease, and to determine if the active principle of the plant is eliminated through the milk. The outbreaks occurred at beginning of the raining season, when the plant sprouts ahead other forages, or after the end of the raining season, when M. rigida stayed green and other forages had dried. In the experimental reproduction of the poisoning doses of 10 and 20g of M. rigida per kg body weight from two different regions were lethal to 3 goats and 3 sheep. One goat that ingested 20g/kg and a sheep that ingested 10g/kg recovered. Two sheep and two goats that ingested 5g/kg had mild clinical signs and recovered. Clinical signs of experimental and spontaneous cases were ingurgitation of the jugular veins, reluctance to move, sternal recumbence, incoordination, respiratory distress, depression, instability, and muscular tremors. Death occurred after a clinical manifestation period of about 4 min to 27h40min. The main lesions were pulmonary edema and vacuolization and necrosis of epithelial cells in some renal tubules. To test if the active principle of M. rigida causes sudden deaths in newborn lambs and kids, 2g/kg of the plant were given daily to two goats and five sheep in the 15 days previous to parturition. One sheep aborted two lambs, 5 days before parturition. The four lambs of the other four sheep ingested the colostrum without problems. The kid from one goat ingested the colostrum and died suddenly 5 minutes after. The kid from the other goat died immediately after parturition before ingestion of colostrum...(AU)

Intoxicação experimental por Ipomoea asarifolia (Convolvulaceae) em caprinos e ovinos / Experimental poisoning by Ipomoea asarifolia (Convolvulaceae) in goats and sheep

Ipomoea asarifolia causa uma síndrome tremorgênica em ovinos, caprinos, bovinos e búfalos. Este experimento teve como objetivos determinar a toxicidade para caprinos de I. asarifolia verde, colhidas nas épocas de chuva e de estiagem, e da planta seca triturada, determinar a toxicidade da planta para ovinos, e determinar se o princípio ativo da planta é eliminado pelo leite em doses tóxicas para os cordeiros. No primeiro experimento a planta fresca colhida na época de estiagem e na época de chuvas foi administrada a 16 caprinos. A planta colhida na estiagem foi tóxica na dose diária de 5 e 10g por kg de peso animal (g/kg). A planta colhida na época de chuva foi tóxica na dose diária de 20 e 30g/kg, demonstrando que a planta é mais tóxica durante o período seco. A planta seca, colhida na época de estiagem foi administrada a 9 caprinos em doses diárias de 1.7, 2, 3.4 e 5.1g/kg. Doses de 3, 4 e 5.1g/kg causaram sinais clínicos, demonstrando que a planta mantém a toxicidade após a secagem. A planta fresca colhida na época de estiagem e na época de chuvas foi administrada a 10 ovinos. A planta colhida na estiagem foi tóxica na dose diária de 5g/kg e na época de chuva foi tóxica nas doses de 10 e 20g/kg. Estes resultados sugerem a maior susceptibilidade dos ovinos à intoxicação do que os caprinos. Como alguns produtores mencionam que cordeiros lactentes que não estão pastando se intoxicam através do leite, I. asarifolia foi administrada diariamente nas doses de 2.5, 5 e 10g/kg a 5 ovelhas, a partir do dia do parto (2 ovelhas), do último dia de prenhez (1 ovelha) e 60 dias antes da parição (2 ovelhas). As ovelhas, mas não os cordeiros, apresentaram sinais clínicos, sugerindo que o princípio ativo da planta não é eliminado no leite ou colostro em doses tóxicas para os cordeiros. Em um ovino eutanasiado não foram observadas lesões macroscópicas nem histológicas. Os achados ultra-estruturais mais significativos foram encontrados nos dendritos das...(AU)

Ipomoea asarifolia causes a tremogenic syndrome in sheep, goats, cattle and buffaloes. The objectives of the experiments were (1) to determine the toxicity to goats of fresh I. asarifolia collected during the raining and the dry season, and the toxicity of the dried plant, and (2) to determine the toxicity of the plant to sheep, and if the active principle is eliminated through the milk. In the first experiment the plant collected in the dry season and in the raining season was fed to 16 goats. The plant collected during the dry season caused clinical signs at the daily doses of 5g and 10g/kg body weight. The plant collected during the raining season was toxic at daily doses of 20g and 30g/kg, indicating that the plant is more toxic during the dry season. The plant collected in the dry season and dried was fed to 9 goats at doses of 1.7g, 2.0g, 3.4g, and 5.1g per kg. Daily doses of 3.0g, 4.0g and 5.1g/kg caused clinical signs, showing that the plant maintains its toxicity after being dried. In the second experiment the fresh plant collected in the dry and in the raining season was fed to 10 sheep. The plant collected in the dry season was toxic at the dose of 5g/kg, and the plant collected in the raining season was toxic at the doses of 10g and 20g/kg. The experimental results suggest that sheep are more susceptible to the poisoning than goats. As some farmers mentioned that suckling non-grazing lambs are poisoned by milk ingestion, I. asarifolia was fed at daily doses of 2.5g, 5.0g and 10g/kg for variable periods to 5 sheep from the day of parturition (2 sheep), after the last day of pregnancy (1 sheep) and 60 days before parturition (2 sheep). The sheep but not the lambs showed clinical signs of intoxication suggesting that the active principle is not eliminated through the milk at doses toxic for the lambs. In one euthanized sheep no gross or histologic lesions were detected. The main ultra-structural findings were found in Purkinje...(AU)