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1.
Proc Natl Acad Sci U S A ; 116(47): 23698-23704, 2019 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-31690656

RESUMO

Pyrophosphate deficiency may explain the excessive vascular calcification found in children with Hutchinson-Gilford progeria syndrome (HGPS) and in a mouse model of this disease. The present study found that hydrolysis products of ATP resulted in a <9% yield of pyrophosphate in wild-type blood and aortas, showing that eNTPD activity (ATP → phosphate) was greater than eNPP activity (ATP → pyrophosphate). Moreover, pyrophosphate synthesis from ATP was reduced and pyrophosphate hydrolysis (via TNAP; pyrophosphate → phosphate) was increased in both aortas and blood obtained from mice with HGPS. The reduced production of pyrophosphate, together with the reduction in plasma ATP, resulted in marked reduction of plasma pyrophosphate. The combination of TNAP inhibitor levamisole and eNTPD inhibitor ARL67156 increased the synthesis and reduced the degradation of pyrophosphate in aortas and blood ex vivo, suggesting that these combined inhibitors could represent a therapeutic approach for this devastating progeroid syndrome. Treatment with ATP prevented vascular calcification in HGPS mice but did not extend longevity. By contrast, combined treatment with ATP, levamisole, and ARL67156 prevented vascular calcification and extended longevity by 12% in HGPS mice. These findings suggest a therapeutic approach for children with HGPS.


Assuntos
Trifosfato de Adenosina/análogos & derivados , Trifosfato de Adenosina/metabolismo , Fosfatase Alcalina/fisiologia , Doenças da Aorta/prevenção & controle , Apirase/antagonistas & inibidores , Calcinose/prevenção & controle , Difosfatos/metabolismo , Levamisol/uso terapêutico , Progéria/tratamento farmacológico , Pirofosfatases/antagonistas & inibidores , Trifosfato de Adenosina/uso terapêutico , Fosfatase Alcalina/antagonistas & inibidores , Animais , Antígenos CD/fisiologia , Doenças da Aorta/enzimologia , Apirase/deficiência , Apirase/fisiologia , Calcinose/enzimologia , Modelos Animais de Doenças , Técnicas de Introdução de Genes , Humanos , Lamina Tipo A/genética , Longevidade/efeitos dos fármacos , Masculino , Camundongos , Camundongos Transgênicos , Miócitos de Músculo Liso/metabolismo , Diester Fosfórico Hidrolases/deficiência , Diester Fosfórico Hidrolases/fisiologia , Progéria/genética , Progéria/metabolismo , Progéria/patologia , Pirofosfatases/deficiência , Pirofosfatases/fisiologia , Interferência de RNA , RNA Interferente Pequeno/farmacologia , Reação em Cadeia da Polimerase em Tempo Real
2.
Medicine (Baltimore) ; 98(22): e15927, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31145359

RESUMO

INTRODUCTION: A network meta-analysis was conducted to regard the effects of available immunosuppressive medications in pediatric frequently-relapsing nephrotic syndrome (FRNS) and steroid-dependent nephrotic syndrome (SDNS). METHODS: We reviewed systematically 26 randomized controlled trials (1311 patients) that compared any of the following immunosuppressive agents to placebo/nontreatment (P/NT) or another drug for FRNS/SDNS treatment in children. RESULTS: The main outcomes were efficacy and acceptability. At the 6-month, cyclophosphamide, chlorambucil, levamisole, and rituximab had better efficacy than P/NT (odds ratio [OR]: 0.09, 0.03, 0.28, and 0.07, respectively); cyclophosphamide was significantly more effective than azathioprine and chlorambucil. At 12 months, cyclophosphamide, chlorambucil, cyclosporine, levamisole, and rituximab had better efficacy than P/NT (0.10, 0.03, 0.10, 0.23, and 0.07, respectively); Chlorambucil were found to be more efficacious than levamisole and MMF (0.12 and 0.09, respectively). At 24 months, cyclophosphamide, chlorambucil, and levamisole had better efficacy than P/NT (0.09, 0.04, and 0.03, respectively); cyclophosphamide had better efficacy than cyclosporine and vincristine (0.17 and 0.39, respectively). CONCLUSION: No significant differences in acceptability were found. Our results suggest that cyclophosphamide may be preferred initially in children with FRSN/SDNS, chlorambucil, and rituximab may be acceptable medications for patients with FRSN/SDNS. Long-term follow-up trials focused on gonadal toxicity and limitation of maximum dosage of cyclophosphamide should been carried out.


Assuntos
Glucocorticoides/uso terapêutico , Imunossupressores/uso terapêutico , Síndrome Nefrótica/tratamento farmacológico , Adolescente , Azatioprina/uso terapêutico , Criança , Pré-Escolar , Clorambucila/uso terapêutico , Ciclofosfamida/uso terapêutico , Ciclosporina/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Lactente , Levamisol/uso terapêutico , Masculino , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Rituximab/uso terapêutico , Prevenção Secundária/métodos , Resultado do Tratamento
3.
J Formos Med Assoc ; 118(8): 1193-1201, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30922614

RESUMO

BACKGROUND/PURPOSE: Physicians' and dentists' knowledge of levamisole-induced agranulocytosis or pancytopenia remains incomplete. This study aimed to evaluate the treatment effectiveness of levamisole plus prednisolone on oral lichen planus (OLP) patients with emphasis on levamisole-induced hematological changes. METHODS: Ninety patients with erosive OLP were given 120 mg/day new levamisole (Levazol) and 15 mg/day prednisolone for three consecutive days each week. Three cases with levamisole-induced blood-cytopenias were assessed and treated within one year. RESULTS: Most patients reported significant pain relief and showed no evidence of erosive OLP after 4-8 weeks of treatment with few side effects; nevertheless, three female patients developed agranulocytosis or granulocytopenia with concomitant thrombocytopenia or pancytopenia within 2-6 weeks after levamisole (Levazol) treatment. One case with previously unknown double episodes of agranulocytosis revealed her first episode following interruption of levamisole (Decaris) treatment for 4 months. High fever and sore throat were the most common symptoms, but two agranulocytosis cases remained asymptomatic one week before diagnosis, and were treated with levamisole withdrawal and empiric antimicrobial initiation as well as utilization of granulocyte colony-stimulating factors. Neutrophil recovery took about 1 week, but over 4 weeks in one of the cases (an elderly patient) with septic shock. CONCLUSION: Agranulocytosis or pancytopenia usually developed within 2 months after levamisole treatment, but it might be delayed. Agranulocytosis was more likely to occur in females and onset was acute. Levamisole is an effective immunomodulator for OLP patients; however, it should be used with caution and administered with regular blood monitoring.


Assuntos
Adjuvantes Imunológicos/efeitos adversos , Agranulocitose/induzido quimicamente , Levamisol/efeitos adversos , Líquen Plano Bucal/tratamento farmacológico , Pancitopenia/induzido quimicamente , Adjuvantes Imunológicos/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Levamisol/uso terapêutico , Masculino , Pessoa de Meia-Idade , Prednisolona/uso terapêutico , Resultado do Tratamento
4.
J Fish Dis ; 42(3): 405-412, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30659617

RESUMO

This study evaluated the efficacy of albendazole, ivermectin, levamisole, mebendazole and praziquantel on monogeneans of Colossoma macropomum, based on in vitro and in vivo assays. In vitro assays indicated that albendazole (500, 100, 1,500 and 2,000 mg/L), ivermectin (200, 250, 300 and 350 mg/L) and levamisole (50, 75, 100 and 125 mg/L) were 100% effective against Anacanthorus spatulatus, Notozothecium janauachensis, Mymarothecium boegeri and Linguadactyloides brinkmanni, while mebendazole (125, 150, 175 and 200 mg/L) and praziquantel (5, 10, 15 and 20 mg/L) were ineffective. Fish mortality in 24 hr therapeutic baths with 500 mg/L of albendazole was 6.6%, but the behaviour of the animals remained unchanged, while 200 mg/L of ivermectin caused lethargy, signs of hypoxia and 100% mortality within 2 hr, and 125 mg/L of levamisole caused no mortality. The efficacy of 500 mg/L of albendazole was 48.6% in the 24 hr baths, while that of 125 mg/L levamisole was 88.2%. Although ivermectin showed in vitro efficacy, the lowest concentration used in baths was highly toxic to fish. Therefore, we recommend the use of 125 mg/L of levamisole to control and treat monogenean infestations on C. macropomum in fish farming.


Assuntos
Albendazol/uso terapêutico , Anti-Helmínticos/uso terapêutico , Caraciformes , Ivermectina/uso terapêutico , Levamisol/uso terapêutico , Infecções por Trematódeos/veterinária , Albendazol/efeitos adversos , Animais , Anti-Helmínticos/efeitos adversos , Aquicultura , Doenças dos Peixes/tratamento farmacológico , Doenças dos Peixes/mortalidade , Doenças dos Peixes/parasitologia , Ivermectina/efeitos adversos , Levamisol/efeitos adversos , Trematódeos/efeitos dos fármacos , Infecções por Trematódeos/tratamento farmacológico
5.
Microb Pathog ; 128: 162-170, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30583021

RESUMO

Currently, there is no satisfactory treatment modality available for cutaneous leishmaniasis (CL). The major objective of the present study was to explore the effect of immunomodulator-levamisole in combination with Glucantime in end-stage unresponsive patients with anthroponotic CL (ACL). Twenty end-stage unresponsive patients with ACL were identified for participation in this single-group trial study. Simultaneously, each patient was received a combination of levamisole pills along with Glucantime during the remedy course. Several in vitro complementary experiments were performed to evaluate the mode of action of levamisole and Glucantime alone and in combination using a macrophage model, in vitro MTT assay, flow cytometry and quantitative real time PCR (qPCR). Overall, 75% of the patients showed complete clinical cure, 10% partially improved and the remaining (15%) had underlying chronic diseases demonstrated no response to the treatment regimen. In in vitro studies, there was no cytotoxic effect associated with these drugs in the range of our experiments. The findings by the flow cytometric analysis represented that the highest apoptotic values corresponded to the drugs combination (32.23%) at 200 µg/ml concentration. Finally, the gene expression level of IL-12 p40, iNOS and TNF-α promoted while the level of IL-10 and TGF-ß genes reduced as anticipated. The findings clearly indicated that the combination of levamisole and Glucantime should be considered in end-stage unresponsive patients with ACL who have not responded to basic treatments. The immunomodulatory role of levamisole in mounting immune system as documented by the in vitro experiments and further substantiated by this single-group trail study was highlighted.


Assuntos
Leishmaniose Cutânea/tratamento farmacológico , Levamisol/farmacologia , Levamisol/uso terapêutico , Antimoniato de Meglumina/farmacologia , Antimoniato de Meglumina/uso terapêutico , Adolescente , Adulto , Idoso , Animais , Antiprotozoários/farmacologia , Antiprotozoários/uso terapêutico , Linhagem Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Criança , Doença Crônica/terapia , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Interleucina-10/metabolismo , Subunidade p40 da Interleucina-12/metabolismo , Leishmania tropica/efeitos dos fármacos , Leishmania tropica/patogenicidade , Levamisol/administração & dosagem , Macrófagos/efeitos dos fármacos , Masculino , Antimoniato de Meglumina/administração & dosagem , Camundongos , Pessoa de Meia-Idade , Óxido Nítrico Sintase Tipo II/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/metabolismo , Adulto Jovem
6.
Kidney Int ; 95(1): 210-218, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30497684

RESUMO

Both levamisole and mycophenolate mofetil (MMF) prevent relapses in patients with frequently relapsing nephrotic syndrome; however, their efficacy has not been compared prospectively. This single-center, randomized, open-label trial enrolled 149 children ages 6-18 years with frequently relapsing or steroid-dependent nephrotic syndrome. Participants were randomized in a 1:1 ratio to receive therapy with MMF (750-1000 mg/m2 daily) or levamisole (2-2.5 mg/kg on alternate days) for 1 year; prednisolone was discontinued by 2-3 months. In intention-to-treat analyses, the frequency of relapse was similar between participants treated with MMF and levamisole (mean difference -0.29 relapses/patient-year; 95% confidence interval -0.65, 0.08). Relapse rates declined to almost one-third of baseline for both treatment groups. Therapy with MMF was not superior to levamisole in terms of the proportions of participants with sustained remission (40.8% vs. 34.2%), frequent relapses (14.5% vs. 16.4%), or treatment failure, a composite outcome of frequent relapses, steroid resistance, or significant steroid toxicity (15.8% vs. 20.6%). These outcomes were also similar in time to event analyses. Changes in anthropometry and blood pressure were similar between the groups, and the rates of adverse effects were low in both groups. Flow cytometry in 32 participants demonstrated similar proportions of B cells and CD4+, CD8+, T helper (Th)1, Th2, Th17, and T regulatory (Treg) cells during follow-up. Therapy with MMF was not superior to levamisole in the frequency of relapses, likelihood of sustained remission or corticosteroid sparing in children with frequently relapsing or steroid-dependent nephrotic syndrome. Registration CTRI/2012/02/002394.


Assuntos
Glucocorticoides/farmacologia , Imunossupressores/uso terapêutico , Levamisol/uso terapêutico , Ácido Micofenólico/uso terapêutico , Síndrome Nefrótica/tratamento farmacológico , Adolescente , Criança , Resistência a Medicamentos , Feminino , Glucocorticoides/uso terapêutico , Humanos , Masculino , Síndrome Nefrótica/patologia , Estudos Prospectivos , Recidiva , Resultado do Tratamento
7.
Zh Nevrol Psikhiatr Im S S Korsakova ; 119(12): 106-114, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31994523

RESUMO

Levamisole is an immunomodulatory drug which can trigger development of levamisole-induced multifocal inflammatory leukoencephalopathy (LIMIL) in patients treated for helminthic invasion, aphthous stomatitis, cancer, or cocaine users. LIMIL clinical case in patient 45 years old after single dose of levamisole (taken without any medical prescription) was described. We presented clinical history and clinical picture, MRI and laboratory data and treatment results during 1-year observation. According to similarity of LIMIL with acute disseminating encephalomyelitis or debut of multiple sclerosis and high frequency of levamisole usage in Russia (usually without medical prescription) LIMIL should be included in differential diagnosis in demyelinating disorders and treated according to current clinical recommendation.


Assuntos
Adjuvantes Imunológicos/efeitos adversos , Doenças Desmielinizantes , Leucoencefalopatia Multifocal Progressiva/induzido quimicamente , Levamisol/efeitos adversos , Adjuvantes Imunológicos/uso terapêutico , Humanos , Levamisol/uso terapêutico , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Federação Russa
8.
J Zoo Wildl Med ; 49(4): 893-901, 2018 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-30592931

RESUMO

Over a 2-yr period, four Goeldi's monkeys ( Callimico goeldii) died in a private zoo due to infections with the spirurid nematode Pterygodermatites nycticebi. Therapeutic measures with different anthelmintics were not successful. Due to the severe consequences caused by these infections, different actions were initiated, including sanitation measures and controlling of potential intermediate hosts (coprophagous arthropods). To identify possible intermediate hosts, arthropod species detected in the enclosure-parasite-free German cockroaches ( Blattella germanica), European earwigs ( Forficula auricularia), and rough woodlice ( Porcellio scaber)-were experimentally fed with feces of monkeys with patent P. nycticebi infections, resulting in established infections with third-stage larvae (L3) in roaches and earwigs. Furthermore, spiruroid L3 were detectable in 43% of the roaches and 30% of earwigs caught at the zoo. Polymerase chain reaction and sequence analysis of eggs, larval, and adult stages resulted in identical results, confirming the establishment of the parasite's life cycle in the zoo. This is the first documentation of the vector capacity of the European earwigs for P. nycticebi. As a measure of sanitation, a large part of the enclosure was emptied and cleaned. The Goeldi's monkeys were quarantined and treated with levamisole (7.5 mg/kg sc twice in intervals of 2 wk). Repeated coprologic examinations by zinc chloride flotation were undertaken. After the levamisole therapy, eggs were not found in the feces for 3 mo. However, shortly after resettling the monkeys into the sanitized enclosure, reshedding of small amounts of spirurid eggs was observed, whereupon deworming with levamisole was prescribed several times per year. The sanitation measures and the elimination of the intermediate hosts in a natural enclosure are presented as an example of the long-term controlling of the parasites.


Assuntos
Antinematódeos/uso terapêutico , Callimico , Levamisol/uso terapêutico , Doenças dos Macacos/prevenção & controle , Doenças dos Macacos/transmissão , Infecções por Spirurida/veterinária , Espirurídios/fisiologia , Animais , Animais de Zoológico , Blattellidae/crescimento & desenvolvimento , Blattellidae/parasitologia , Feminino , Insetos Vetores/crescimento & desenvolvimento , Insetos Vetores/parasitologia , Insetos/crescimento & desenvolvimento , Insetos/parasitologia , Larva/parasitologia , Masculino , Ninfa/parasitologia , Infecções por Spirurida/prevenção & controle , Infecções por Spirurida/transmissão , Suíça
9.
Cutis ; 102(3): 169;170;175;176, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30372707

RESUMO

Reports of levamisole-induced vasculopathy (LIV) secondary to use of levamisole-contaminated cocaine largely have been limited to the skin. We report the case of a 35-year-old woman with painful purpuric lesions affecting the cheeks, nose, ears, arms, and legs of several days' duration. She recently had used crack cocaine. A biopsy of a lesion on the right arm demonstrated leukocytoclastic vasculitis. She also reported abdominal pain and gastric reflux of recent onset but denied any history of gastrointestinal tract disease. An upper gastrointestinal endoscopy was performed and demonstrated hemorrhagic erosions of the esophagus and stomach similar in appearance to the cutaneous lesions. Because dermatologists often are the specialists making the diagnosis of LIV, it is important they inform other involved clinicians that the skin may not be the sole repository of vascular insult.


Assuntos
Transtornos Relacionados ao Uso de Cocaína/patologia , Cocaína Crack/efeitos adversos , Levamisol/efeitos adversos , Gastropatias/patologia , Estômago/patologia , Vasculite/patologia , Adulto , Transtornos Relacionados ao Uso de Cocaína/etiologia , Contaminação de Medicamentos , Feminino , Humanos , Levamisol/uso terapêutico , Púrpura/induzido quimicamente , Púrpura/patologia , Estômago/irrigação sanguínea , Gastropatias/induzido quimicamente , Vasculite/induzido quimicamente
10.
Parasitol Res ; 117(12): 3993-4002, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30302586

RESUMO

The aim of the present study was to evaluate the effects of treatment with different anthelmintic compounds on the productivity of naturally infected calves and the economic viability of these treatments within extensive breeding systems employing different nutritional strategies after weaning. For this purpose, 4 farms with 42-60 calves naturally infected with gastrointestinal nematodes were selected. The calves were distributed into 6 groups (7-10 animals each) per farm and treated with ivermectin 1%, ivermectin 3.15%, eprinomectin 5%, levamisole 7.5%, albendazole 15%, and control group (no treatment). These animals were evaluated over an experimental period of 150 days. Levamisole 7.5% presented the best capacity for the reduction of eggs per gram (EPG) of feces in all herds evaluated, followed by albendazole 15% and eprinomectin 5%. Parasite resistance to multiple drugs was found in all herds, especially those of Cooperia, Haemonchus, Oesophagostomum, and Trichostrongylus. For farm 1, differences in weight gain and EPG reduction percentages led to a difference of US$285.06 between the levamisole and ivermectin 3.15% groups. Similar findings were noted for the levamisole and ivermectin 1% groups of farm 3, with a difference of US$399.37 because of the final weight gain in these groups. For farms 2 and 4, the ivermectin 3.15% and control groups, respectively, were the most profitable; these unexpected results were possibly influenced by variables not measured during the experimental period. This study suggested that anthelmintic treatments should always precede an efficacy test, once they are demonstrated to be most profitable under adequate breeding conditions, to ensure adequate control of gastrointestinal nematode infection.


Assuntos
Anti-Helmínticos/uso terapêutico , Doenças dos Bovinos/tratamento farmacológico , Haemonchus/efeitos dos fármacos , Infecções por Nematoides/tratamento farmacológico , Infecções por Nematoides/veterinária , Oesophagostomum/efeitos dos fármacos , Carne Vermelha/parasitologia , Trichostrongylus/efeitos dos fármacos , Albendazol/uso terapêutico , Animais , Bovinos , Doenças dos Bovinos/parasitologia , Fezes/parasitologia , Hemoncose/tratamento farmacológico , Hemoncose/veterinária , Ivermectina/análogos & derivados , Ivermectina/uso terapêutico , Levamisol/uso terapêutico , Esofagostomíase/tratamento farmacológico , Esofagostomíase/veterinária , Contagem de Ovos de Parasitas/veterinária , Tricostrongilose/tratamento farmacológico , Tricostrongilose/veterinária , Desmame
11.
BMJ Case Rep ; 20182018 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-30232205

RESUMO

Cocaine adulterated levamisole is an increasingly reported cause of skin necrosis, arthralgia and systemic vasculitis, but renal involvement is uncommon. We present a case of a 40-year-old Hispanic man with a history of cocaine abuse who presented with acute kidney injury to the rheumatology clinic where he was being treated for chronic inflammatory arthritis. He was found to have a serum creatinine of 2.5 mg/dL, microscopic haematuria and subnephrotic proteinuria, along with positive proteinase 3, myeloperoxidase, anticardiolipin antibodies and an elevated antinuclear antibody titre. The renal pathology revealed focal necrotising glomerulonephritis with crescentic features and mild immune type deposition. The patient was treated with cocaine abstinence, pulse dose steroids followed by maintenance prednisone, rituximab and cyclophosphamide. His renal function subsequently improved but did not normalise. We believe that his incomplete improvement was due to the degree of kidney injury on presentation as well as recidivism with cocaine use.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/induzido quimicamente , Cocaína/antagonistas & inibidores , Glomerulonefrite/induzido quimicamente , Glomerulosclerose Segmentar e Focal/induzido quimicamente , Levamisol/efeitos adversos , Lesão Renal Aguda/diagnóstico , Lesão Renal Aguda/etiologia , Adulto , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Antinematódeos/uso terapêutico , Cocaína/efeitos adversos , Creatinina/sangue , Glomerulonefrite/patologia , Glomerulosclerose Segmentar e Focal/tratamento farmacológico , Glomerulosclerose Segmentar e Focal/patologia , Hematúria/complicações , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Levamisol/uso terapêutico , Masculino , Proteinúria/complicações , Esteroides/administração & dosagem , Esteroides/uso terapêutico , Resultado do Tratamento
12.
J Dermatol Sci ; 92(1): 38-44, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30143369

RESUMO

BACKGROUND: Erythema multiforme major (EMM) is an immune-mediated mucocutaneous eruption mostly triggered by herpes simplex virus (HSV) infection. A vicious circle of recurrence may be developed due to HSV reactivation and prolonged use of systemic corticosteroids to control EMM. Levamisole is an immunomodulator and has been applied to prevent relapses of recurrent HSV infection. OBJECTIVE: To evaluate the clinical efficacy and safety of levamisole in patients with recalcitrant recurrent EMM. METHODS: We enrolled 23 patients with recurrent EMM treated with levamisole and 24 controls, and analyzed the demographics, treatments and outcomes. RESULTS: Patients with recurrent EMM for years (mean 3.99 ± 2.71) showed significantly reduced recurrences after various durations of levamisole treatment (recurrences after and before treatment: 3.98 ± 1.04 vs 6.75 ± 1.45 times per year, p = 1.33x10-8). The recurrences of EMM also significantly reduced after levamisole treatment comparing to that of patients without levamisole treatment (p = 3.77x10-9). No patient was reported to have severe side effects during or after levamisole treatment. CONCLUSIONS: Levamisole was effective in reducing recurrences of recalcitrant recurrent EMM and can thus be considered an alternative or add-on therapy for this disorder.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Eritema Multiforme/tratamento farmacológico , Levamisol/uso terapêutico , Adjuvantes Imunológicos/efeitos adversos , Corticosteroides/uso terapêutico , Adulto , Antivirais/uso terapêutico , Estudos de Casos e Controles , Quimioterapia Combinada , Eritema Multiforme/diagnóstico , Eritema Multiforme/imunologia , Feminino , Humanos , Levamisol/efeitos adversos , Masculino , Pessoa de Meia-Idade , Recidiva , Indução de Remissão , Resultado do Tratamento , Adulto Jovem
13.
Saudi J Kidney Dis Transpl ; 29(3): 591-597, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29970735

RESUMO

Levamisole is often discussed as the first alternative to steroids. It is an antihelminthic drug that has been used for steroid-sensitive nephrotic syndrome (SSNS) for more than 20 years. Interleukin (IL)-18, a member of the IL-1 cytokine superfamily, is recognized as an important regulator of immune responses. The aim of the study was to investigate the IL-18 levels in serum from children with SSNS during relapse and remission after using levamisole or three months in a trial to test the efficacy of its action in reducing frequency of relapses in SSNS. This study was done on 23 children with frequently relapsing SSNS treated with levamisole besides steroids, then followed up three months; 16 males and seven females (mean age: 7.96 years and median 8 years). Clinical and laboratory assessments were done before starting therapy and after three months including cumulative dose of steroids and serum IL-18. We found that IL-18 level showed a significant elevation after three months of levamisole therapy compared to its level before initiation of levamisole therapy, with no relapses in these three months, no reported side effect, and significant reduction of cumulative dose of steroids. Levamisole effectiveness in reduction of relapses of SSNS may be due to resetting of the type 1/type 2 imbalance, proved by induction of IL 18 may be useful in the therapy.


Assuntos
Anti-Inflamatórios/uso terapêutico , Interleucina-18/sangue , Levamisol/uso terapêutico , Síndrome Nefrótica/sangue , Síndrome Nefrótica/tratamento farmacológico , Pressão Sanguínea/fisiologia , Criança , Feminino , Humanos , Masculino , Síndrome Nefrótica/epidemiologia , Esteroides
14.
J Med Case Rep ; 12(1): 209, 2018 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-30008268

RESUMO

BACKGROUND: Levamisole belongs to the antihelminthic class of drugs that are sometimes administered to patients with frequently relapsing or steroid-dependent nephrotic syndrome, owing to its steroid-sparing effects. Neutropenia and skin lesions, compatible with vasculitis, have been reported as drug complications, but they are rarely associated with any systemic involvement. CASE PRESENTATION: We report a case of a 9-year-old Arab boy with steroid-dependent nephrotic syndrome who was treated with levamisole after his third relapse. The drug was initially well tolerated, but mild isolated neutropenia occurred 6 months after levamisole administration. This was followed by cutaneous vasculitis of both ears and the left cheek. The patient also developed hepatosplenomegaly and anemia. Levamisole was discontinued, and his disease remained in remission. All the systemic manifestations disappeared gradually over the course of 1 month. The patient remained in remission until 1 year after levamisole withdrawal, when clinical nephrosis recurred. CONCLUSIONS: Despite levamisole's being a useful drug for maintaining remission in steroid-dependent nephrotic syndrome, patients on long-term levamisole therapy should be monitored closely to prevent serious complications that can easily be resolved by simple drug withdrawal.


Assuntos
Adjuvantes Imunológicos/efeitos adversos , Levamisol/efeitos adversos , Síndrome Nefrótica/tratamento farmacológico , Vasculite/induzido quimicamente , Adjuvantes Imunológicos/uso terapêutico , Bochecha/irrigação sanguínea , Bochecha/patologia , Criança , Orelha/irrigação sanguínea , Orelha/patologia , Glucocorticoides/uso terapêutico , Humanos , Levamisol/uso terapêutico , Masculino , Necrose
15.
Medicine (Baltimore) ; 97(24): e10975, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29901586

RESUMO

RATIONALE: Parasitic eosinophilic meningitis is rarely observed in infants. The diagnosis of this disease is complicated by its atypical and severe clinical manifestations. PATIENT CONCERNS: An infant presented to our hospital with high fever and irritability, as well as refusal to walk. Cerebrospinal fluid collected through lumbar puncture showed increased eosinophil count and third-stage Angiostrongylus cantonensis larvae. DIAGNOSES: Eosinophilic meningitis was suspected. INTERVENTIONS: We started empiric treatment with levamisole (14 mg bid, 2.5 mg/kg·day) and prednisone (17.5 mg qd, 1.5 mg/kg·day). OUTCOMES: All of the infant's symptoms were resolved approximately 72 hours after treatment. The patient fully recovered from her illness after completing 4 weeks of levamisole and prednisolone treatment. LESSONS: A. cantonensis is the most common cause of parasitic eosinophilic meningitis cases in Southeast Asia. Physicians treating infants who live in areas where A. cantonensis is endemic and who present with irritability, abnormal motor function, and elevated eosinophil count should be aware of the disease to provide timely and rational therapy to the patients.


Assuntos
Eosinofilia/complicações , Meningite/etiologia , Infecções por Strongylida/complicações , Angiostrongylus cantonensis , Animais , Antinematódeos/uso terapêutico , Feminino , Glucocorticoides/uso terapêutico , Humanos , Lactente , Levamisol/uso terapêutico , Meningite/diagnóstico , Meningite/tratamento farmacológico , Infecções por Strongylida/diagnóstico , Infecções por Strongylida/tratamento farmacológico
16.
Contrib Nephrol ; 195: 131-142, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29734158

RESUMO

Amelioration of podocyte injury, which can lead to podocyte detachment, is the target of therapeutic intervention in glomerular diseases. Since podocytes are terminally differentiated cells with little or no proliferative ability, their loss results in permanent glomerular dysfunction. In immune-mediated glomerular diseases, a variety of immunomodulatory agents are used to maintain podocytes by systemic immunosuppression, which indirectly ameliorates podocyte injury by interrupting the input of immunological stress. However, in contrast to the indirect therapeutic strategy mediated by immunosuppression, recent data now suggest that immunomodulatory agents directly act on podocytes in an agent-dependent manner. Indeed, the therapeutic efficacy of immunomodulatory agents is, at least in part, derived by the direct action on podocytes. In this review, we discuss the molecular targets and mechanisms by which immunomodulatory agents alleviate podocyte injury and examine their clinical significance.


Assuntos
Imunossupressores/farmacologia , Podócitos/efeitos dos fármacos , Abatacepte/farmacologia , Abatacepte/uso terapêutico , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/uso terapêutico , Inibidores de Calcineurina/farmacologia , Inibidores de Calcineurina/uso terapêutico , Everolimo/farmacologia , Everolimo/uso terapêutico , Glomerulonefrite/tratamento farmacológico , Glomerulonefrite/imunologia , Glomerulonefrite/patologia , Glomerulonefrite Membranosa/tratamento farmacológico , Glomerulonefrite Membranosa/imunologia , Glomerulonefrite Membranosa/patologia , Glomerulosclerose Segmentar e Focal/tratamento farmacológico , Glomerulosclerose Segmentar e Focal/imunologia , Glomerulosclerose Segmentar e Focal/patologia , Glucocorticoides/farmacologia , Glucocorticoides/uso terapêutico , Humanos , Fatores Imunológicos/farmacologia , Fatores Imunológicos/uso terapêutico , Imunossupressores/uso terapêutico , Levamisol/farmacologia , Levamisol/uso terapêutico , Ácido Micofenólico/farmacologia , Ácido Micofenólico/uso terapêutico , Nefrose Lipoide/tratamento farmacológico , Nefrose Lipoide/imunologia , Nefrose Lipoide/patologia , Síndrome Nefrótica/tratamento farmacológico , Síndrome Nefrótica/imunologia , Síndrome Nefrótica/patologia , Podócitos/imunologia , Podócitos/patologia , Ribonucleosídeos/farmacologia , Ribonucleosídeos/uso terapêutico , Rituximab/farmacologia , Rituximab/uso terapêutico , Sirolimo/farmacologia , Sirolimo/uso terapêutico , Serina-Treonina Quinases TOR/antagonistas & inibidores , Tacrolimo/farmacologia , Tacrolimo/uso terapêutico
17.
Biom J ; 60(4): 815-826, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29790186

RESUMO

In clinical trials with time-to-event outcomes, it is of interest to predict when a prespecified number of events can be reached. Interim analysis is conducted to estimate the underlying survival function. When another correlated time-to-event endpoint is available, both outcome variables can be used to improve estimation efficiency. In this paper, we propose to use the convolution of two time-to-event variables to estimate the survival function of interest. Propositions and examples are provided based on exponential models that accommodate possible change points. We further propose a new estimation equation about the expected time that exploits the relationship of two endpoints. Simulations and the analysis of real data show that the proposed methods with bivariate information yield significant improvement in prediction over that of the univariate method.


Assuntos
Biometria/métodos , Ensaios Clínicos como Assunto , Neoplasias do Colo/tratamento farmacológico , Fluoruracila/uso terapêutico , Humanos , Levamisol/uso terapêutico , Modelos Estatísticos , Fatores de Tempo , Resultado do Tratamento
18.
Rev Bras Parasitol Vet ; 27(1): 27-32, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29641796

RESUMO

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.


Assuntos
Antinematódeos/uso terapêutico , Duddingtonia , Gastroenteropatias/veterinária , Levamisol/uso terapêutico , Infecções por Nematoides/veterinária , Doenças dos Ovinos/parasitologia , Doenças dos Ovinos/terapia , Animais , Brasil , Terapia Combinada , Feminino , Gastroenteropatias/parasitologia , Gastroenteropatias/terapia , Masculino , Infecções por Nematoides/terapia , Ovinos
19.
Vet Parasitol ; 251: 56-62, 2018 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-29426477

RESUMO

A replicated field trial was conducted to measure the effect on liveweight gain of failing to adequately control anthelmintic resistant populations of Cooperia oncophora and to determine whether populations, and hence production losses, increased with time. Eight mobs of 10 Friesian-Hereford calves were run on independent farmlets from January to December, over each of two years. All mobs were routinely treated with a pour-on formulation of eprinomectin every six weeks, which controlled parasites other than Cooperia. Four mobs also received six weekly treatments with an oral levamisole plus albendazole combination anthelmintic to control Cooperia. Liveweights, condition scores, faecal egg counts and larval numbers on pasture were measured throughout. In the first year animals treated with eprinomectin alone were 12.9 kg lighter in November than those treated with eprinomectin plus albendazole and levamisole, however, in the second year there was no difference between the treatment groups. The data, therefore, support the view that while C. oncophora is less pathogenic than other cattle parasite species it can still cause production losses when present in sufficient numbers. In the first year of the study, parasite load, as measured by faecal nematode egg count and larval numbers on herbage, tended to be higher and calf growth rates lower than in the second year. In both years, counts of infective larvae on herbage declined over winter-spring to be at low levels before mid-summer. This suggests that the carry-over of infection from one crop of calves to the next was relatively small and hence that the level of challenge to the young calves at the start of each year was largely due to the effectiveness of the quarantine treatments administered when the animals arrived on the trial site. Low survival of larvae on pasture between grazing seasons, resulting in small larval populations on pasture when drenching programmes start each summer, might help to explain the widespread development of anthelmintic resistance in this parasite under New Zealand grazing systems.


Assuntos
Anti-Helmínticos/administração & dosagem , Bovinos/parasitologia , Trichostrongyloidea/efeitos dos fármacos , Tricostrongiloidíase/veterinária , Ganho de Peso/efeitos dos fármacos , Albendazol/administração & dosagem , Albendazol/uso terapêutico , Animais , Anti-Helmínticos/uso terapêutico , Doenças dos Bovinos/tratamento farmacológico , Doenças dos Bovinos/epidemiologia , Doenças dos Bovinos/parasitologia , Ivermectina/administração & dosagem , Ivermectina/análogos & derivados , Larva/efeitos dos fármacos , Levamisol/administração & dosagem , Levamisol/uso terapêutico , Nova Zelândia/epidemiologia , Contagem de Ovos de Parasitas , Carga Parasitária , Tricostrongiloidíase/tratamento farmacológico , Tricostrongiloidíase/epidemiologia
20.
Vet Parasitol Reg Stud Reports ; 13: 224-227, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-31014879

RESUMO

Routine faecal examination of a herd of weaned male goats revealed heavy infections with gastrointestinal strongyles (GIS) and Strongyloides sp. Moxidectin (routinely dosed at 0.3 mg·kg-1, i.e., 1.5 times the sheep dose), although fully effective against GIS, failed to control Strongyloides sp., with an estimated faecal egg count reduction (FECR) of only 55.5%. In addition, levamisole (11.25 mg·kg-1) and ivermectin (0.3 mg·kg-1) also failed to control Strongyloides sp., with FECRs of 1.4% and 53.5%, respectively. On the other hand, albendazole (7.5 mg·kg-1) and netobimin (11.25 mg·kg-1 and 22.5 mg·kg-1) reduced by 96.3-99.9% the Strongyloides sp. faecal egg counts according to dose and remained effective, although, in the past, this drug family has been used extensively on the same farm and was no longer effective against GIS. Albendazole or netobimin at 3 times the dose for sheep may be effective for Strongyloides sp. control in case of severe infection.


Assuntos
Anti-Helmínticos/uso terapêutico , Surtos de Doenças/veterinária , Doenças das Cabras/tratamento farmacológico , Strongyloides/efeitos dos fármacos , Estrongiloidíase/veterinária , Fatores Etários , Albendazol/uso terapêutico , Animais , Anti-Helmínticos/administração & dosagem , Resistência a Medicamentos , Fezes/parasitologia , Doenças das Cabras/parasitologia , Cabras/parasitologia , Guadalupe/epidemiologia , Ivermectina/uso terapêutico , Levamisol/uso terapêutico , Macrolídeos/uso terapêutico , Masculino , Contagem de Ovos de Parasitas/veterinária , Estrongiloidíase/epidemiologia , Resultado do Tratamento , Clima Tropical
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