Economic impact of gastrointestinal nematodes in Morada Nova sheep in Brazil / Impacto econômico de nematódeos gastrintestinais em ovinos Morada Nova no Brasil

Abstract This study evaluated the economic impact of gastrointestinal nematode (GIN) infection in Morada Nova lambs under different parasite chemical control conditions. For this, 246 lambs, in the rainy and dry season, were randomized into groups according to their anthelmintic treatment with levamisole: control (CT: no treatment); routine treatment (RT: treated every 42 days); and targeted selective treatment (TST: treated according to the average daily weight gain, DWG). From 63 days of age (D63) to D210, the lambs were weighed and monitored for GIN infection parameters. Spending on anthelmintics in the production system was 1.3% of the total economic result. The economic result per animal (R$ 5.00 = US$ 1.00) was higher in the RT group, amounting to US$ 6.60 in the rainy and US$ 5.69 in the dry season, due to higher DWG. Thus, RT presented economic results 14.4% and 10.9% higher than CT, and 7.2% and 1.9% higher than TST, in the rainy and dry season, respectively. However, fast development of resistance made RT unfeasible. Here, the economic impact of GIN infection on a national scale is discussed, demonstrating its importance and the impossibility of profitable and sustainable sheep production without adequate control.

Resumo Este estudo avaliou o impacto econômico da infecção por nematoides gastrintestinais (NGI), em cordeiros Morada Nova, sob diferentes condições de controle químico dos parasitas. Para isso, 246 cordeiros, na estação chuvosa e seca, foram randomizados em grupos de acordo com o tratamento com levamisol: controle (TC: sem tratamento); tratamento rotineiro (TR: tratado a cada 42 dias); e tratamento seletivo direcionado (TST: tratado de acordo com o ganho de peso médio diário, GMD). Dos 63 dias de idade (D63) ao D210, os cordeiros foram pesados ​​e monitorados quanto aos parâmetros de infecção por NGI. O gasto com anti-helmínticos no sistema produtivo foi de 1,3% do resultado econômico total. O resultado econômico por animal (R$ 5,00 = US$ 1,00) foi maior no grupo RT, totalizando US$ 6,60 na estação chuvosa e US$ 5,69 na seca, devido ao maior GMD. Assim, o RT apresentou resultados econômicos 14,4% e 10,9% superiores ao TC, e 7,2% e 1,9% superiores ao TST, no período chuvoso e seco, respectivamente. Entretanto o rápido desenvolvimento de resistência inviabiliza o TR. O impacto econômico da infecção por NGI em escala nacional são aqui discutidos, demonstrando sua importância e a impossibilidade de uma ovinocultura lucrativa e sustentável sem o controle adequado.

Pyoderma gangrenosum associated to the use of cocaine/levamisole. Series of three cases and literature review

Abstract Pyoderma gangrenosum associated to the use of cocaine/levamisole is a rare condition associated to their consumption. Cocaine use is frequent in Colombia, and the substance is contaminated with levamisole, an anthelmintic that increases the psychotropic effects and enhances its side effects. We present three clinical cases of patients with ulcerated lesions, in which the diagnosis was pyoderma gangrenosum secondary to the use of cocaine contaminated with levamisole. This called the attention of the health staff to investigate the abuse of substances in gangrenous pyoderma and also evidence that the interruption of consumption was the basis of management.

Agranulocitosis febril y artropatía reactiva asociada a consumo de cocaína en un paciente HLA B27 positivo / Febrile agranulocytosis and reactive arthropathy associated with cocaine consumption in an HLA B27 positive patient

Resumen La agranulocitosis asociada al consumo de cocaína es un fenómeno vinculado a la presencia de levamisol, un agente antihelmíntico e inmunomodulador, usado como adulterante de la cocaína. Esta reacción puede presentarse con mayor frecuencia en personas con HLA B27. Además de la agranulocitosis, las personas que consumen cocaína adulterada con levamisol pueden desarrollar fiebre, lesiones en piel, artralgias y, menos frecuentemente, artritis y entesitis inflamatoria. Presentamos el caso de un paciente consumidor de cocaína, con genotipo HLA B27, que desarrolló agranulocitosis febril y artropatía reactiva. En sangre se detectó la presencia de ANCA p, ANCA atípico y MPO, y fueron excluidas otras causas de agranulocitosis. Fue tratado con corticoides y posteriormente metotrexato, terapia de deshabituación, con buena evolución.

Abstract Agranulocytosis associated with cocaine use is a phenomenon linked to the presence of levamisole, an anthelminthic and immunomodulating agent, used as an adulterant to cocaine. This reaction has been associated with the presence of HLA B27. In addition to agranulocytosis, people who use levamisole-adulterated cocaine may develop fever, skin lesions, arthralgias, and less frequently, inflammatory enthesitis and arthritis. We present the case of a cocaine-consuming patient with HLA B27 genotype, who developed febrile agranulocytosis and inflammatory arthropathy. The presence of p ANCA, atypical ANCA and MPO was detected in blood, and other causes of agranulocytosis were excluded. He was treated with corticosteroids and later methotrexate, therapy for addiction, with good evolution.

Anthelmintic activity of nanoencapsulated carvacryl acetate against gastrointestinal nematodes of sheep and its toxicity in rodents / Atividade anti-helmíntica do acetato de carvacrila nanoencapsulado sobre nematoides gastrintestinais de ovinos e toxicidade em roedores

Abstract The objective of this study was to evaluate the efficacy of carvacryl acetate (CVA) and nanoencapsulated CVA (nCVA) on gastrointestinal nematodes of sheep. The CVA was nanoencapsulated with chitosan/gum arabic and the efficacy of nanoencapsulation (EE), yield, zeta potential, nanoparticle morphology and release kinetics at pH 3 and 8 were analyzed. Acute and subchronic toxicity were evaluated in rodents and reduction of egg counts in the faeces (FECRT) of sheep. The sheep were divided into four groups (n = 10): G1, 250 mg/kg CVA; G2, 250 mg/kg nCVA; G3, polymer matrix and G4: 2.5 mg/kg monepantel. EE and nCVA yield were 65% and 57%, respectively. The morphology of the nanoparticles was spherical, size (810.6±286.7 nm), zeta potential in pH 3.2 (+18.3 mV) and the 50% release of CVA at pHs 3 and 8 occurred at 200 and 10 h, respectively. nCVA showed LD50 of 2,609 mg/kg. CVA, nCVA and monepantel reduced the number of eggs per gram of faeces (epg) by 57.7%, 51.1% and 97.7%, respectively. The epg of sheep treated with CVA and nCVA did not differ from the negative control (P>0.05). Nanoencapsulation reduced the toxicity of CVA; however, nCVA and CVA presented similar results in the FECRT.

Resumo O objetivo deste trabalho foi avaliar a eficácia do acetato de carvacrila (ACV) e do ACV nanoencapsulado (nACV) sobre nematóides gastrintestinais de ovinos. O ACV foi nanoencapsulado com quitosana/goma arábica e foi analisada a eficácia de nanoencapsulamento (EE), o rendimento, potencial zeta, morfologia das nanopartículas e cinética de liberação em pH 3 e 8. Foram avaliadas as toxicidades aguda e subcrônica em roedores e a redução da contagem de ovos nas fezes (RCOF) de ovinos. Os ovinos foram divididos em quatro grupos (n = 10): G1, 250 mg/kg ACV; G2, 250 mg/kg de nACV; G3, matriz polimérica e G4: 2,5 mg/kg de monepantel. A EE e o rendimento de nACV foram de 65% e 57%, respectivamente. A morfologia das nanopartículas foi esférica, tamanho (810,6±286,7 nm), potencial zeta no pH 3,2 (+18,3 mV) e a liberação de 50% de CVA nos pHs 3 e 8 ocorreu às 200 e 10 h, respectivamente. nACV apresentou DL50 de 2.609 mg/kg. ACV, nACV e o monepantel reduziram a contagem de ovos por grama de fezes (opg) em 57,7%, 51,1% e 97,7%, respectivamente. A contagem de opg de ovelhas tratadas com ACV e nCVA não diferiu do controle negativo (P>0,05). O nanoencapsulamento reduziu a toxicidade do AVC; no entanto, nACV e ACV apresentaram resultados semelhantes na RCOF.

High concentration of levamisole in the diet of Colossoma macropomum (Pisces: Serrasalmidae) is effective for controlling monogenean parasites / Alta concentração de levamisol na dieta de Colossoma macropomum (Pisces: Serrasalmidae) é efetiva para controlar parasitos monogenea

Abstract This study investigated the effects of diets supplemented with levamisole on monogeneans on the gills of Colossoma macropomum. Fish were fed with diets containing levamisole at concentrations of 0, 300, 600, 900 and 1200 mg kg-1 for 24, 96 and 240 h and the infection by Anacanthorus spatulatus, Notozothecium janauachensis and Mymarothecium boegeri were evaluated. None of the levamisole concentrations caused either mortality or behavioral alterations in fishes during 240 h of feeding. After 24 h of feeding with 1200 mg kg-1 of levamisole, the abundance of N. janauachensis decreased in comparison with treatments of 0, 300, 600 and 900 mg kg-1, as did the abundance of M. boegeri after 240 h of feeding with 1200 mg kg-1 of levamisole. The efficacy of 900 mg kg-1 of levamisole was only 55.7% after 96 h of feeding, but it was 84.6% after 240 h of feeding with 1200 mg kg-1. Our results show that 1200 mg kg-1 of levamisole for 10 days has good anthelmintic efficacy against monogeneans of C. macropomum. Since monogeneans elicit some of the worst problems in C. macropomum, this study has provided evidence of an effective control method that may be used in fish farms.

Resumo Este estudo investigou os efeitos de dietas suplementadas com levamisol na infecção por monogeneas nas brânquias de Colossoma macropomum. Os peixes foram alimentados com dietas contendo 0, 300, 600, 900 e 1200 mg kg-1 de levamisol por 24, 96 e 240 h e os níveis de infecção por Anacanthorus spatulatus, Notozothecium janauachensis e Mymarothecium boegeri, foram avaliados. Nenhuma das concentrações de levamisol causou mortalidade ou alterações comportamentais nos peixes durante 240 h de alimentação. Após 24 h de alimentação com 1.200 mg kg-1 de levamisol, a abundância de N. janauachensis diminuiu quando comparada aos tratamentos com 0, 300, 600 e 900 mg kg-1, bem como a abundância de M. boegeri após 240 h de alimentação com 1200 mg kg-1 de levamisol. A eficácia de 900 mg kg-1 de levamisol foi somente de 55,7% após 96 h de alimentação, mas foi de 84,6% após 240 h de alimentação com 1200 mg kg-1. Os resultados mostram que 1200 mg kg-1 de levamisol durante 10 dias, tem uma boa eficácia antihelmíntica contra monogeneas de C. macropomum. Como monogeneas provocam alguns dos piores problemas em C. macropomum, este estudo forneceu evidências de um método de controle eficaz que pode ser usado em pisciculturas.

Adulterants in crack cocaine in Brazil / Adulterantes no crack vendido na "Cracolândia"

Abstract Introduction Brazil is the world's biggest consumer of crack cocaine, and dependence is a major public health issue. This is the first study to investigate the prevalence of potentially harmful adulterants present in hair samples from Brazilian patients with crack cocaine dependence. Method We evaluated adulterants in hair samples extracted by convenience from 100 patients admitted at the 48 hour-observation unit of Centro de Referência de Álcool, Tabaco e Outras Drogas (CRATOD), Brazil's largest center for addiction treatment. A cross-sectional analysis was performed with the data obtained. Results Adulterants were found in 97% of the analyzed hair samples. The most prevalent adulterant was lidocaine (92%), followed by phenacetin (69%) and levamisole (31%). Conclusion Adulterants were widely prevalent in hair samples from crack users treated at CRATOD: at least one adulterant was present in virtually all the hair samples collected. This points to a need to monitor adverse effects in the clinical setting in order to provide this high-risk group of patients with prompt and effective care related to the acute and chronic complications associated with these adulterants.

Resumo Introdução O Brasil é o maior consumidor mundial de crack, e a dependência é um grande problema de saúde pública. Este é o primeiro estudo a investigar a prevalência de adulterantes potencialmente nocivos presentes em amostras de cabelo de pacientes brasileiros com dependência de crack. Métodos Foram avaliados adulterantes em amostras de cabelos extraídos por conveniência de 100 pacientes internados na unidade de observação de 48 horas do Centro de Referência de Álcool, Tabaco e Outras Drogas (CRATOD), o maior centro de tratamento de dependência do Brasil. Uma análise transversal foi realizada com os dados obtidos. Resultados Foram encontrados adulterantes em 97% das amostras de cabelo analisadas. O adulterante mais prevalente foi a lidocaína (92%), seguida da fenacetina (69%) e levamisol (31%). Conclusão Os adulterantes foram amplamente prevalentes em amostras de cabelo de usuários de crack tratados no CRATOD: pelo menos um adulterante estava presente em praticamente todas as amostras de cabelo coletadas. Isso aponta para a necessidade de monitorar os efeitos adversos no ambiente clínico, a fim de proporcionar a esse grupo de pacientes de alto risco cuidados imediatos e efetivos relacionados às complicações agudas e crônicas associadas a esses adulterantes.

Control of sheep gastrointestinal nematodes using the combination of Duddingtonia flagrans and Levamisole Hydrochloride 5% / Controle de nematódeos gastrintestinais de ovinos utilizando a combinação de Duddingtonia flagrans e Cloridrato de Levamisole 5%

Abstract The objective was to evaluate the action of D. flagrans pellets in association with Levamisole Hydrochloride 5% for controlling sheep gastrointestinal nematodes in the northeastern Brazil. Three groups of six sheep each were formed: group 1 received 3 g of the pellets (0.6 g of D. flagrans mycelium) for each 10 kg b.w., twice a week for six months, and deworming with Levamisole Hydrochloride 5% when EPG ≥ 1500; group 2 received a dosage of Levamisole Hydrochloride 5% when EPG ≥ 1500; and group 3 received 3 g of pellets without fungi for each 10 kg b.w., twice a week for six months. EPG counts, larval cultures, packed cell volume (PCV) and weighing were performed every 15 days; monthly, samples of grass from each paddock were collected. The mean EPG of the groups began to statistically differ from day 30 (p < 0.05). Group 1 required less deworming with Levamisole Hydrochloride 5% and showed superiority of PCV values ​​throughout the experiment (p < 0.05). There was a significant reduction (p < 0.05) in L3 recovery in the group 1 paddock from day 30 onwards. The use of D. flagrans pellets in association with Levamisole Hydrochloride 5% was effective for controlling gastrointestinal nematodes.

Resumo O objetivo foi avaliar a ação de péletes de Duddingtonia flagrans em associação ao Cloridrato de Levamisole 5% no controle de nematódeos gastrintestinais de ovinos no Nordeste do Brasil. Foram formados três grupos de seis animais cada: grupo 1 recebeu 3 g de péletes (0,6 g de micélio de D. flagrans) para cada 10 kg p.v., duaz vezes por semana durante seis meses, e vermifugações com Cloridrato de Levamisole 5% quando OPG > 1500; grupo 2 recebeu uma dosagem de Cloridrato de Levamisole 5% quando OPG ≥ 1500; e grupo 3 recebeu 3 g de péletes sem fungos para cada 10 kg de p.v., duas vezes por semana durante seis meses. Contagens de OPG, coproculturas, de volumes globulares (VG) e pesagens foram realizadas a cada 15 dias. Mensalmente, amostras de pasto de cada piquete eram coletadasa. A média de OPG dos grupos começou a diferir estatisticamente a partir do dia 30 (p < 0,05). O grupo 1 necessitou de menos vermifugações com Cloridrato de Levamisole 5% e demonstrou superioridade nos valores de VG durante todo o experimento (p < 0,05). Houve redução significativa (p < 0,05) nas L3 recuperadas no piquete do grupo 1 a partir do dia 30. Em conclusão, a utilização de péletes de D. flagrans em associação ao Cloridrato de Levamisole 5% foi eficaz no controle de nematódeos gastrintestinais de ovinos.

In vitro susceptibility of nematophagous fungi to antiparasitic drugs: interactions and implications for biological control / Suscetibilidade in vitro de fungos nematófagos à antiparasitários: interações e implicações para o controle biológico

Abstract The fast anthelmintic resistance development has shown a limited efficiency in the control of animal's endoparasitosis and has promoted research using alternative control methods. The use of chemicals in animal anthelmintic treatment, in association with nematophagous fungi used for biological control, is a strategy that has proven to be effective in reducing the nematode population density in farm animals. This study aims to verify the in vitro susceptibility of the nematophagous fungi Arthrobotrys oligospora, Duddingtonia flagrans and Paecilomyces lilacinus against the antiparasitic drugs albendazole, thiabendazole, ivermectin, levamisole and closantel by using the Minimum Inhibitory Concentration (MIC). MICs ranged between 4.0 and 0.031 µg/mL for albendazole, thiabendazole and ivermectin, between 0.937 and 0.117 µg/mL for levamisole, and between 0.625 and 0.034 µg/mL for closantel. The results showed that all antiparasitic drugs had an in vitro inhibitory effect on nematophagous fungi, which could compromise their action as agents of biological control. D. flagrans was the most susceptible species to all drugs.

Resumo O desenvolvimento rápido da resistência anti-helmíntica demonstrou a eficiência limitada no controle de endoparasitoses em animais, e promoveu a investigação em métodos de controles alternativos. O uso de produtos químicos no tratamento anti-helmíntico animal, em associação com fungos nematófagos utilizados para o controlo biológico, é uma estratégia que tem provado ser eficaz na redução da densidade da população de nematódeos em animais agrícolas. Este estudo teve como objetivo verificar a suscetibilidade in vitro dos fungos nematófagos Arthrobotrys oligospora, Duddingtonia flagrans e Paecilomyces lilacinus frente aos antiparasitários albendazol, tiabendazol, ivermectina, levamisol e closantel, usando a concentração inibitória mínima (MIC). Os MICs variaram entre 4,0 e 0,031 μg/mL para albendazol, tiabendazol e ivermectina, entre 0,937 e 0,117 μg/mL para o levamisol, e entre 0,625 e 0,034 μg/mL para closantel. Os resultados mostraram que todos os antiparasitários tiveram um efeito inibidor in vitro sobre os fungos nematófagos, o que poderia comprometer suas atividades como agentes de controle biológico. D. flagrans foi a espécie mais sensível a todas as drogas.

Influence of dexamethasone and levamisole on macrophage recruitment, giant cell formation and blood parameters in the tropical fish Piaractus mesopotamicus / Influência da dexametasona e levamisol no recrutamento de macrófagos, formação de células gigantes e parâmetros hematológicos no peixe tropical Piaractus mesopotamicus

The aim of this study was to evaluate the effect of parenteral administration of dexamethasone and levamisole on the accumulation of macrophages and formation of giant cells in chronic inflammation by foreign body and blood parameters in pacu (Piaractus mesopotamicus). It was used 50 mg/kg of levamisole and 2.0 mg/kg of dexamethasone and the combination of both drugs. Coverslips were implanted under the skin. After 2, 7, and 15 days postimplantation (DPI), fish were anesthetized for removal of coverslips and the number of macrophages and giant cells were count. It was also collected blood from the caudal vessel to evaluate: red blood cell count, hematocrit, hemoglobin concentration, leukocytes count, thrombocytes count, MCV, and MCHC. We observed that dexamethasone affects negatively the formation of giant cells in the chronic inflammation for foreign body. Levamisole, despite being immunostimulatory in several species, showed limited action. However, it was enough to counteract the effect of dexamethasone; the association of the drugs did not interfere significantly in erythrocyte and leukocyte number in most of the treatments and times studied. In dexamethasone group there was a reduction in the number of erythrocytes and hemoglobin associated with increased mean corpuscular volume, suggesting slight macrocytic anemia. At 15 DPI, most groups showed the recovery of hematologic response. As in mammals, dexamethasone affects negatively the inflammatory response. Levamisole showed little effect by itself. However, in some parameters the association of both drugs causes similar response to control and naïve groups, showing the antagonistic effect of these drugs.

O objetivo deste estudo foi avaliar o efeito da administração parenteral de dexametasona e levamisol na acumulação de macrófagos e formação de células gigantes na inflamação crônica por corpo estranho e avaliação de parâmetros sanguíneos em pacu (Piaractus mesopotamicus). Utilizou-se 50 mg/kg de levamisol e 2,0 mg / kg de dexametasona e a combinação de ambos fármacos. As lamínulas foram implantadas sob a pele. Depois de 2, 7 e 15 dias pós-implantação (DPI), os peixes foram anestesiados para a remoção das lamínulas e contagem do número de macrófagos e células gigantes. Foi coletado sangue da veia caudal para realizar contagem de células vermelhas, leucócitos, trombócitos, concentração de hemoglobina, MCV e MCHC. Observou-se que a dexametasona afeta negativamente a formação de células gigantes na inflamação crónica por corpo estranho. O levamisol, apesar de ser considerado imunoestimulante em várias espécies, mostrou ação limitada. No entanto, foi suficiente para neutralizar o efeito da dexametasona; a associação das drogas não interferiu significativamente no número de eritrócitos e de leucócitos na maioria dos tratamentos e períodos estudados. No grupo da dexametasona, houve redução do número de eritrócitos e concentração de hemoglobina associado ao aumento do volume corpuscular médio sugerindo leve anemia macrocítica. Aos 15 DPI, a maioria dos grupos mostrou recuperação na resposta hematológica. Como em mamíferos, a dexametasona afeta negativamente a resposta inflamatória. O levamisol mostrou pouco efeito por si só. No entanto, em alguns parâmetros a associação das duas drogas provoca resposta similar ao grupo controle e naive, mostrando o efeito antagonista de estas drogas.

Cocaína adulterada con levamisol: reporte de tres casos clínicos / Levamisole-adulterated cocaine: a report on three clinical cases

El consumo de clorhidrato y pasta base de cocaína en Uruguay tiene una prevalencia de vida del 6,9% y 0,7% respectivamente. Las complicaciones tóxicas secundarias al consumo dependen de la concentración del alcaloide así como de la presencia de adulterantes. El levamisol, antihelmíntico veterinario, reconocido adulterante de la cocaína en Estados Unidos (2003), fue detectado en Uruguay en el año 2013. Este adulterante genera complicaciones tales como neutropenia, vasculitis cutánea, glomerulonefritis, hemorragia pulmonar y leucoencefalopatía. Se describen los tres primeros casos clínicos de complicaciones por levamisol como adulterante de cocaína reportados al Centro de Información y Asesoramiento Toxicológico. Los pacientes eran consumidores crónicos con edades entre los 35 y 40 años. En los tres casos se objetivó un púrpura retiforme con centro necrótico asociado a anticuerpos ANCA positivos con tendencia a presentarse en lóbulos de orejas, mejillas y extremidades, tal como se reporta en las vasculitis por levamisol. Se reportó neutropenia asociada en un caso. Los tres pacientes presentaron anemia. Dos casos presentaron falla renal aguda. El tratamiento principal fue el cese del consumo, lo que produjo una reversión completa de las complicaciones. Todos requirieron debridación o injertos de piel, o ambos. Se discuten y analizan las complicaciones mencionadas así como el riesgo que conlleva la reexposición y los tratamientos propuestos para las mismas, tales como los factores de crecimiento de granulocitos, antibióticos de amplio espectro y los corticoides. Se requiere un alto índice de sospecha para vincular estas manifestaciones clínicas a la presencia de levamisol como adulterante de la cocaína.

Consumption of cocaine hydrochloride and cocaine base paste (CBP) in Uruguay has a lifetime prevalence of 6.9% and 0.7% respectively. Complications associated to toxic side effects of cocaine abuse depend on the concentration of the alkaloid, as well as on the presence of adulterants. Levamisole, a veterinary anthelmintic, a well know cocaine adulterant in the US was identified in Uruguay in 2013. This adulterant results in complications such as neutropenia, skin vasculitis, glomerulonephritis and leukoencephalopathy. The study describes the first three clinical cases of complications resulting from cocaine cut with levamisole reported to the Toxicology Center for Information and Counseling. The patients included were chronic cocaine abusers between 35 and 40 years old. Retiform purpura was detected in the three cases with a necrotic center associated to ANCA antibodies, with a tendency to appear in the earlobes, cheeks, and limbs, as it is reported in levamisole associated vasculitis. Neutropenia was reported in one case. The three patients had anemia. Two of the cases presented acute kidney failure. The main treatment was interruption of consumption, what resulted in a complete reversion of complications. All patients required debridement or skin grafts, or both. The above mentioned complications are discussed and analyzed, as well as the risk re-exposure and the suggested treatments involve, as the granulocytes growth factors, broad spectrum antibiotics and corticoids. A high degree of suspicion is required to associate these clinical manifestations to the presence of levamisole as a cocaine adulterant.

O consumo de cloridrato e pasta base de cocaína no Uruguai tem uma prevalência de vida de 6,9% e 0,7% respectivamente. As complicações tóxicas secundarias ao consumo dependem da concentração do alcaloide como também da presença de adulterantes. O levamisol, anti-helmíntico veterinário, um conhecido adulterante da cocaína nos Estados Unidos (2003), foi detectado no Uruguai em 2013. Este adulterante gera complicações tais como neutropenia, vasculite cutânea, glomerulonefrite, hemorragia pulmonar e leucoencefalopatia. Os três primeiros casos clínicos de complicações por levamisol como adulterante de cocaína informados ao Centro de Información y Asesoramiento Toxicológico são descritos. Os pacientes eram consumidores crônicos com idades entre 35 e 40 anos. Nos três casos se observou púrpura retiforme com centro necrótico associado a anticorpos ANCA positivos com tendência a apresentação nos lóbulos das orelhas, bochechas e extremidades, como estão descritas nas vasculites por levamisol. Em um caso foi observada neutropenia. Três pacientes apresentaram anemia e dois falha renal aguda. O tratamento principal foi a cessação do consumo com reversão total das complicações. Foi necessário realizar debridação ou enxertos de pele, ou ambos em todos os casos. As complicações mencionadas bem como o risco vinculado à reposição e os tratamentos propostos para as mesmas, como por exemplo os fatores de crescimento de granulócitos, antibióticos de amplio espectro e corticoides, são discutidos e analisados. É necesssário um alto índice de suspeita para vincular estas manifestações clínicas à presença de levamisol como adulterante da cocaína.

Cocaine/levamisole-induced systemic vasculitis with retiform purpura and pauci-immune glomerulonephritis

Levamisole has been increasingly used as an adulterant of cocaine in recent years, emerging as a public health challenge worldwide. Levamisole-associated toxicity manifests clinically as a systemic vasculitis, consisting of cutaneous, hematological, and renal lesions, among others. Purpura retiform, cutaneous necrosis, intravascular thrombosis, neutropenia, and less commonly crescentic nephritis have been described in association with anti-neutrophil cytoplasmic antibodies (ANCAs) and other autoantibodies. Here we report the case of a 49-year-old male who was a chronic cocaine user, and who presented spontaneous weight loss, arthralgia, and 3 weeks before admission purpuric skin lesions in the earlobes and in the anterior thighs. His laboratory tests on admission showed serum creatinine of 4.56 mg/dL, white blood count 3,800/μL, hemoglobin 7.3 g/dL, urinalysis with 51 white blood cells/μL and 960 red blood cells/μL, and urine protein-to-creatinine ratio 1.20. Serum ANCA testing was positive (>1:320), as well as serum anti-myeloperoxidase and anti-proteinase 3 antibodies. Urine toxicology screen was positive for cocaine and levamisole, with 62.8% of cocaine, 32.2% of levamisole, and 5% of an unidentified substance. Skin and renal biopsies were diagnostic for leukocytoclastic vasculitis and pauci-immune crescentic glomerulonephritis, respectively. The patient showed a good clinical response to cocaine abstinence, and use of corticosteroids and intravenous cyclophosphamide. Last serum creatinine was 1.97 mg/dL, white blood cell count 7,420/μL, and hemoglobin level 10.8 g/dL. In levamisole-induced systemic vasculitis, the early institution of cocaine abstinence, concomitant with the use of immunosuppressive drugs in severe cases, may prevent permanent end organ damage and associate with better clinical outcomes.

Retiform Purpura Caused by the Use of Cocaine, That Was Probably Adulterated with Levamisole

No abstract available.

Efficacy and Safety of Mycophenolate Mofetil in Children with Steroid Dependent Nephrotic Syndrome

PURPOSE: Steroid dependent nephrotic syndrome (SDNS) is a chronic illness in childhood hard to treat. Steroid sparing drugs are often used, because long-term steroid therapy can cause severe side effects. We studied to compare efficacy between MMF and other drugs including cyclosporine and levamisole. METHODS: This study was performed retrospectively on patients with SDNS, who were treated at Pusan National University Children's hospital. MMF group included 11 patients who were treated with MMF for at least six months between June 2012 and July 2014. As control groups, cyclosporine group (n=15) and levamisole group (n=18) included patients treated between January 2008 and July 2014. Number of relapse was analyzed in patients treated more than six months, and relapse free for one year was analyzed in patients treated more than one year. RESULTS: In MMF group, ten were boys and mean age at onset was 5.8 years. Mean age at starting of MMF was 8.6 years. Number of relapse in MMF group was reduced significantly after treatment from 3.4 /year to 0.2 /year (P=0.003). There was no significant difference in number of relapse among groups (MMF: 0.2 /year, cyclosporine: 0.5 /year, levamisole: 0.5 /year). Comparing the early relapse within six months after treatment levamisole group was significantly higher than the other two groups (P=0.04). CONCLUSIONS: MMF which is used in SDNS significantly reduced the relapse and side effects were rare. In addition, MMF did not show any significant difference in comparison with the other two groups in number of relapse and relapse free for one year.

Lupus eritematoso sistémico asociado al consumo crónico de cocaína / Systemic lupus erythematosus associated with chronic cocaine use

El lupus eritematoso sistémico (LES) es una enfermedad autoinmune, de etiología desconocida,que se manifiesta como una enfermedad sistémica pleomórfica, afectando,principalmente, a las mujeres. El mecanismo autoinmune del LES se ha visto asociado aldesarrollo del fenómeno de la célula LE. Este fenómeno consiste en la fagocitosis, por partede los neutrófiflos, de los núcleos liberados por las células opsonizadas por el anticuerpoanti-DNP y el complemento C3b. A partir de diferentes estudios, se ha visto relación multifactorialetiológica en la inducción de enfermedades autoinmunes, en la que se encuentrauna relación infrecuente con el consumo crónico de cocaína. Esto se explica a través deprocesos biológicos en los que se inhibe la fagocitosis de los restos celulares generados pordichas enfermedades. A continuación se presenta el caso de un paciente con antecedentede consumo de derivados de la benzoilecgonina, quien ingresa por manifestaciones constitucionales,pulmonares, renales, cutáneas y musculoesqueléticas, en quien los paraclínicosy la biopsia renal confirman el diagnóstico de LES con nefritis lúpica clase iv. Así mismo, sedestaca la relevancia de sospecha y diagnóstico temprano de dicha enfermedad y la correlacióncon el consumo de cocaína para dar tratamiento oportuno y evitar el progreso y suscomplicaciones...

Assessment of serum interleukin-8 as a sensitive serological marker in monitoring the therapeutic effect of levamisole in recurrent aphthous ulcers: A randomized control study.

Aim: The study was designed to evaluate the serum interleukin‑8 (IL‑8) levels in patients with recurrent aphthous ulcer (RAU) and monitor the immunomodulation and altered IL‑8 levels by levamisole before therapy and after levamisole therapy. Materials and Methods: This study was carried as a randomized case‑control study involving a study group of 30 patients diagnosed as RAUs and given levamisole (vermisole 150 mg, od for 1st 3 days of 3 weeks in a month and for 3 months with a gap of 1 week) and these patients were recalled after 3 months and were subjected for estimation of serum IL‑8 levels. Control group had 20 age and sex matched individuals with no systemic illness and were not given any levamisole. Good compliance was reported at the end of the study. Results: Mild gastric irritation was reported and when severe it was managed by H1 blocker. Patients were reviewed after 3 months. The follow‑up data at each visit with respect to each other and to base‑line values was calibrated using a Students t‑test. Highly significant comparisons were obtained in the serum IL‑8 between study and control groups before the onset of levamisole (t = 6.53, P ≤ 0.001). IL‑8 levels reduced by 72% after levamisole was instituted in RAU patients and comparison was highly significant for before and after levamisole onset (t = 5.54, P ≤ 0.001). Conclusion: This study points to the effectiveness of levamisole as an effective adjunct therapy in the routine management of RAU.

Proposed method for agglutinating antibody titer analysis and its use as indicator of acquired immunity in pacu, Piaractus mesopotamicus / Aglutinante de anticorpos como indicador de imunidade adquirida de pacu Piaractus mesopotamicus

Antibody can be assessed by agglutinating antibody titer which is a quantitative measure of circulating antibodies in serum from fish previously immunized. The antibody evaluation has been performed with different fish species, and is considered a reliable method that can be applied to confirm several hypothesis regarding acquired immunity, even in conjunction with precise methods to describe immune mechanisms. In order to provide appropriate analytical methods for future studies on the specific immune system of native fish, the present study standardized on assay to measure the serum agglutinating antibody titer produced after immunization with inactivated A. hydrophila and levamisole administration in pacu. It was possible to determine the agglutinating antibodies titer in a satisfactorily way in pacu immunized with inactive A. hydrophila, and the highest titers were observed on fish fed with levamisole.

Os anticorpos podem ser avaliados pelo título aglutinante de anticorpos, que é uma medida quantitativa de anticorpos no soro de peixe previamente imunizados. A determinação do título de anticorpos foi realizada com diversas espécies de peixes e é considerado um método confiável que pode ser aplicado para confirmar diversas hipóteses que envolvam o sistema adquirido de defesa, mesmo em conjunto com métodos precisos, para descrever mecanismos imunes. A fim de prover métodos analíticos adequados para futuros estudos sobre o sistema imune específico de peixes nativos, o presente estudo aperfeiçoou o ensaio para avaliar o título aglutinante de anticorpos em soro de pacu imunizados com A. hydrophila e alimentados com levamisol. Foi possível determinar o título aglutinante de anticorpos de forma satisfatória, em pacus imunizados com A. hydrophila inativa, e os maiores títulos foram observados em peixes alimentados com levamisol.