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[PMID]:28468639
[Au] Autor:Sasajima H; Yagi S; Osada H; Zako M
[Ad] Endereço:Department of Ophthalmology, Aichi Medical University, Nagakute, Aichi, Japan.
[Ti] Título:Botulinum toxin-induced acute anterior uveitis in a patient with Behçet's disease under infliximab treatment: a case report.
[So] Source:J Med Case Rep;11(1):124, 2017 May 04.
[Is] ISSN:1752-1947
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Injections of lipopolysaccharide in animal models generate acute anterior uveitis (also known as endotoxin-induced uveitis), but the effects of lipopolysaccharide injection are unknown in humans. We describe an unusual case in which acute anterior uveitis was dramatically activated subsequent to botulinum toxin injection in a patient with Behçet's disease but the acute anterior uveitis was satisfactorily attenuated by infliximab. CASE PRESENTATION: A 53-year-old Japanese man had normal ocular findings at his regularly scheduled appointment. He had been diagnosed as having incomplete-type Behçet's disease 11 years before. Three years after the diagnosis he was given systemic infusions of 5 mg/kg infliximab every 8 weeks and he had not experienced a uveitis attack for 8 years with no treatment other than infliximab. Two days after the eye examination, he received intracutaneous botulinum toxin injections to treat axillary hyperhidrosis on both sides. Three hours after the injections, he noted rapidly increasing floaters in his right eye. Four days after the injections, his right eye showed severe acute anterior uveitis with deteriorated aqueous flare and anterior vitreous opacity. He received his scheduled infliximab injection, and the right acute anterior uveitis immediately attenuated. CONCLUSIONS: Botulinum toxin may have clinical effects similar to those of lipopolysaccharide in endotoxin-induced uveitis models. To the best of our knowledge, this is the first report to suggest that botulinum toxin may trigger acute anterior uveitis, although the precise mechanism is still unclear.
[Mh] Termos MeSH primário: Síndrome de Behçet/tratamento farmacológico
Toxinas Botulínicas/efeitos adversos
Hiperidrose/tratamento farmacológico
Infliximab/administração & dosagem
Neurotoxinas/administração & dosagem
Uveíte/induzido quimicamente
[Mh] Termos MeSH secundário: Seres Humanos
Injeções Subcutâneas
Masculino
Meia-Idade
Tomografia de Coerência Óptica
Uveíte/diagnóstico por imagem
Uveíte/tratamento farmacológico
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Neurotoxins); B72HH48FLU (Infliximab); EC 3.4.24.69 (Botulinum Toxins)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1186/s13256-017-1288-1


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[PMID]:27771241
[Au] Autor:Merino PS; Vera RE; Mariñas LG; Gómez de Liaño PS; Escribano JV
[Ad] Endereço:Ocular Motility Section, Department of Ophthalmology, Hospital General Universitario Gregorio Marañón, Madrid, Spain. Electronic address: pilimerino@gmail.com.
[Ti] Título:Botulinum toxin for treatment of restrictive strabismus.
[So] Source:J Optom;10(3):189-193, 2017 Jul - Sep.
[Is] ISSN:1989-1342
[Cp] País de publicação:Spain
[La] Idioma:eng
[Ab] Resumo:PURPOSE: To study the types of acquired restrictive strabismus treated in a tertiary hospital and the outcome of treatment with botulinum toxin. METHODS: We performed a 10-year retrospective study of patients with restrictive strabismus aged ≥18 years who were treated with botulinum toxin. Treatment was considered successful if the final vertical deviation was ≤5 PD, horizontal deviation ≤10 PD, with no head turn or diplopia. RESULTS: We included 27 cases (mean age, 61.9 years). Horizontal strabismus was diagnosed in 11.1%, vertical in 51.9%, and mixed in 37%. Strabismus was secondary to cataract surgery in 6 cases, high myopia in 6, orbital fractures in 5, retinal surgery in 5, Graves ophthalmopathy in 4, and repair of conjunctival injury in 1 case. Diplopia was diagnosed in all patients, head turn in 33.3%. The initial deviation was 14 PD (range, 2-40), the mean number of injections per patient was 1.6 (range, 1-3), and the mean dose was 9.5 IU (range, 2.5-22.5). At the end of follow-up, diplopia was recorded in 59.3%, head turn in 18.5%, surgical treatment in 51.9%, and need for prism glasses in 14.8%. Outcome was successful in 37% of patients (4 high myopia, 3 orbital fractures, 2 post-surgical retinal detachment, and 1 post-cataract surgery). Mean follow-up was 3±1.8 years. CONCLUSION: Vertical deviation was observed in half of the sample. The most frequent deviation was secondary to cataract surgery and high myopia. Treatment with botulinum toxin was successful in one-third of the patients at the end of follow-up.
[Mh] Termos MeSH primário: Toxinas Botulínicas/administração & dosagem
Movimentos Oculares/fisiologia
Previsões
Estrabismo/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Feminino
Seguimentos
Seres Humanos
Injeções Intramusculares
Masculino
Meia-Idade
Neurotoxinas/administração & dosagem
Músculos Oculomotores
Estudos Retrospectivos
Estrabismo/fisiopatologia
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Neurotoxins); EC 3.4.24.69 (Botulinum Toxins)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE


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[PMID]:29447689
[Au] Autor:Popoff MR
[Ad] Endereço:Bacterial Toxins, Institut Pasteur, Paris, France. Electronic address: mpopoff@pasteur.fr.
[Ti] Título:Botulinum Neurotoxins: Still a Privilege of Clostridia?
[So] Source:Cell Host Microbe;23(2):145-146, 2018 02 14.
[Is] ISSN:1934-6069
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Botulinum neurotoxins (BoNTs) are potent bacterial toxins mostly produced by genetically diverse clostridial strains. Recently, BoNT variants have been reported in non-clostridial strains. In this issue of Cell Host & Microbe, Zhang et al. (2018) describe a novel BoNT in Entecoccus faecium.
[Mh] Termos MeSH primário: Toxinas Botulínicas
Neurotoxinas
[Mh] Termos MeSH secundário: Clostridium
Seres Humanos
Hidrolases
[Pt] Tipo de publicação:JOURNAL ARTICLE; COMMENT
[Nm] Nome de substância:
0 (Neurotoxins); EC 3.- (Hydrolases); EC 3.4.24.69 (Botulinum Toxins)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180216
[St] Status:MEDLINE


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[PMID]:29390585
[Au] Autor:Lee SY; Jeon YT; Kim BR; Han EY
[Ad] Endereço:Department of Rehabilitation Medicine, Jeju National University Hospital, Jeju National University School of Medicine, Jeju, Republic of Korea.
[Ti] Título:Combined treatment of botulinumtoxin and robot-assisted rehabilitation therapy on poststroke, upper limb spasticity: A case report.
[So] Source:Medicine (Baltimore);96(51):e9468, 2017 Dec.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Spasticity is a major complication after stroke, and botulinumtoxin A (BoNT-A) injection is commonly used to manage focal spasticity. However, it is uncertain whether BoNT-A can improve voluntary motor control or activities of daily living function of paretic upper limbs. This study investigated whether BoNT-A injection combined with robot-assisted upper limb therapy improves voluntary motor control or functions of upper limbs after stroke. PATIENT CONCERNS: Two subacute stroke patients were transferred to the Department of Rehabilitation. DIAGNOSES: Patients demonstrated spasticity in the upper extremity on the affected side. INTERVENTIONS: BoNT-A was injected into the paretic muscles of the shoulder, arm, and forearm of the 2 patients at the subacute stage. Conventional rehabilitation therapy and robot-assisted upper limb training were performed during the rehabilitation period. OUTCOMES: Manual dexterity, grip strength, muscle tone, and activities of daily living function were improved after multidisciplinary rehabilitation treatment. LESSONS: BoNT-A injection in combination with multidisciplinary rehabilitation treatment, including robot-assisted arm training, should be recommended for subacute spastic stroke patients to enhance appropriate motor recovery.
[Mh] Termos MeSH primário: Toxinas Botulínicas/uso terapêutico
Espasticidade Muscular/etiologia
Robótica/métodos
Reabilitação do Acidente Vascular Cerebral/métodos
Acidente Vascular Cerebral/complicações
[Mh] Termos MeSH secundário: Adulto
Braço
Terapia Combinada
Feminino
Seres Humanos
Masculino
Meia-Idade
Espasticidade Muscular/reabilitação
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
EC 3.4.24.69 (Botulinum Toxins)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180203
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009468


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[PMID]:29237498
[Au] Autor:Lee DH; Han J; Han SH; Lee SC; Kim M
[Ad] Endereço:Institute of Vision Research, Department of Ophthalmology, Severance Eye and ENT Hospital, Yonsei University College of Medicine, Seoul, South Korea.
[Ti] Título:Vitreous hemorrhage and Rhegmatogenous retinal detachment that developed after botulinum toxin injection to the extraocular muscle: case report.
[So] Source:BMC Ophthalmol;17(1):249, 2017 Dec 13.
[Is] ISSN:1471-2415
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The authors report a case of a rare complication that occurred after botulinum toxin injection to the extraocular muscle, which was easily overlooked and successfully corrected by surgery. CASE PRESENTATION: A 34-year-old female patient visited our clinic for diplopia and ocular motility disorder after removal of an epidermoid tumor of the brain. At her initial visit, her best-corrected visual acuity (BCVA) was 20/20 for both eyes. An alternate cover test showed 45 prism-diopter esotropia and 3 prism-diopter hypertropia in the right eye. Following 6 months of observation, the deviation of the strabismus did not improve, and botulinum toxin was injected into the right medial rectus (RMR). After 6 days, she visited our clinic with decreased visual acuity of her right eye. The BCVA was found to be 20/50 for her right eye. Funduscopic examination presented a retinal tear inferonasal to the optic disc with preretinal hemorrhage. Subretinal fluid nasal to the fovea was seen on optical coherence tomography (OCT). Barrier laser photocoagulation was done around the retinal tear; however, her visual acuity continued to decrease, and vitreous hemorrhage and subretinal fluid at the lesion did not improve. In addition, a newly developed epiretinal membrane was seen on OCT. An alternate cover test presented 30 prism-diopter right esotropia. 19 weeks after RMR botulinum toxin injection, she received pars plana vitrectomy, membranectomy, endolaser barrier photocoagulation, and intravitreal bevacizumab (Avastin®) injection. After 4 months, her visual acuity improved to 20/20, and only 4 prism-diopter of right hypertropia and 3 prism-diopter of exotropia were noted. Vitreous opacity and the epiretinal membrane were completely removed, as confirmed by funduscopic and examination. CONCLUSIONS: Sudden loss of vision after injection of botulinum toxin into the extraocular muscle may suggest a serious complication, and a prompt, thorough ophthalmic examination should be performed. If improvements are not observed, rapid surgical intervention is recommended to prevent additional complications.
[Mh] Termos MeSH primário: Toxinas Botulínicas/efeitos adversos
Neurotoxinas/efeitos adversos
Descolamento Retiniano/induzido quimicamente
Hemorragia Vítrea/induzido quimicamente
[Mh] Termos MeSH secundário: Adulto
Feminino
Seres Humanos
Injeções Intramusculares/efeitos adversos
Injeções Intraoculares/efeitos adversos
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Neurotoxins); EC 3.4.24.69 (Botulinum Toxins)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180105
[Lr] Data última revisão:
180105
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171215
[St] Status:MEDLINE
[do] DOI:10.1186/s12886-017-0649-2


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[PMID]:28455330
[Au] Autor:Fredrick CM; Lin G; Johnson EA
[Ad] Endereço:Department of Bacteriology, University of Wisconsin-Madison, Madison, Wisconsin, USA.
[Ti] Título:Regulation of Botulinum Neurotoxin Synthesis and Toxin Complex Formation by Arginine and Glucose in Clostridium botulinum ATCC 3502.
[So] Source:Appl Environ Microbiol;83(13), 2017 Jul 01.
[Is] ISSN:1098-5336
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Botulinum neurotoxin (BoNT), produced by neurotoxigenic clostridia, is the most potent biological toxin known and the causative agent of the paralytic disease botulism. The nutritional, environmental, and genetic regulation of BoNT synthesis, activation, stability, and toxin complex (TC) formation is not well studied. Previous studies indicated that growth and BoNT formation were affected by arginine and glucose in types A and B. In the present study, ATCC 3502 was grown in toxin production medium (TPM) with different levels of arginine and glucose and of three products of arginine metabolism, citrulline, proline, and ornithine. Cultures were analyzed for growth (optical density at 600 nm [OD ]), spore formation, and BoNT and TC formation by Western blotting and immunoprecipitation and for BoNT activity by mouse bioassay. A high level of arginine (20 g/liter) repressed BoNT production approximately 1,000-fold, enhanced growth, slowed lysis, and reduced endospore production by greater than 1,000-fold. Similar effects on toxin production were seen with equivalent levels of citrulline but not ornithine or proline. In TPM lacking glucose, levels of formation of BoNT/A1 and TC were significantly decreased, and extracellular BoNT and TC proteins were partially inactivated after the first day of culture. An understanding of the regulation of growth and BoNT and TC formation should be valuable in defining requirements for BoNT formation in foods and clinical samples, improving the quality of BoNT for pharmaceutical preparations, and elucidating the biological functions of BoNTs for the bacterium. Botulinum neurotoxin (BoNT) is a major food safety and bioterrorism concern and is also an important pharmaceutical, and yet the regulation of its synthesis, activation, and stability in culture media, foods, and clinical samples is not well understood. This paper provides insights into the effects of critical nutrients on growth, lysis, spore formation, BoNT and TC production, and stability of BoNTs of We show that for ATCC 3502 cultured in a complex medium, a high level of arginine repressed BoNT expression by ca. 1,000-fold and also strongly reduced sporulation. Arginine stimulated growth and compensated for a lack of glucose. BoNT and toxin complex proteins were partially inactivated in a complex medium lacking glucose. This work should aid in optimizing BoNT production for pharmaceutical uses, and furthermore, an understanding of the nutritional regulation of growth and BoNT formation may provide insights into growth and BoNT formation in foods and clinical samples and into the enigmatic function of BoNTs in nature.
[Mh] Termos MeSH primário: Arginina/metabolismo
Toxinas Botulínicas/biossíntese
Botulismo/microbiologia
Clostridium botulinum/genética
Regulação Bacteriana da Expressão Gênica
Glucose/metabolismo
Neurotoxinas/biossíntese
[Mh] Termos MeSH secundário: Proteínas de Bactérias/genética
Proteínas de Bactérias/metabolismo
Toxinas Botulínicas/genética
Clostridium botulinum/crescimento & desenvolvimento
Clostridium botulinum/metabolismo
Seres Humanos
Neurotoxinas/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Neurotoxins); 94ZLA3W45F (Arginine); EC 3.4.24.69 (Botulinum Toxins); IY9XDZ35W2 (Glucose)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171225
[Lr] Data última revisão:
171225
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE


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[PMID]:27773588
[Au] Autor:Srivanitchapoom P; Shamim EA; Diomi P; Hattori T; Pandey S; Vorbach S; Park JE; Wu T; Auh S; Hallett M
[Ad] Endereço:Human Motor Control Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA; Division of Neurology, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand. Electronic address: prachaya.srivanitch
[Ti] Título:Differences in active range of motion measurements in the upper extremity of patients with writer's cramp compared with healthy controls.
[So] Source:J Hand Ther;29(4):489-495, 2016 Oct - Dec.
[Is] ISSN:1545-004X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:STUDY DESIGN: Exploratory case-control study. INTRODUCTION: Writer's cramp (WC) is a type of focal hand dystonia. The central nervous system plays a role in its pathophysiology, but abnormalities in the affected musculoskeletal components may also be relevant. PURPOSE OF THE STUDY: We compared the active range of motion (ROM) in patients with WC and healthy volunteers (HVs) and correlated the findings with disease duration and severity. METHODS: Affected limb joints were measured with goniometers. Patients were assessed at least 3 months after their last botulinum toxin (botulinum neurotoxin) injection, and strength was clinically normal. t tests were used to compare the ROMs of WC with matched HVs. The Spearman correlation coefficient assessed the relationship of active ROMs to the disease duration and handwriting subscore of the Dystonia Disability Scale. RESULTS: ROMs of D1 metacarpophalangeal (MCP) joint extension as well as D2 and D5 MCP flexion were significantly smaller in WC, and distal interphalangeal joint extension in D3 and D5 was significantly greater compared with HVs. There were negative correlations between D2 MCP flexion and disease duration and with Dystonia Disability Scale. DISCUSSION: Abnormalities in ROMs in WC were found. Severity and disease duration correlated with reduced D2 MCP flexion. This may be related to intrinsic biomechanical abnormalities, co-contraction of muscles, or a combination of subclinical weakness and atrophy from repeated botulinum neurotoxin injections. CONCLUSIONS: Hand biomechanical properties should not be ignored in the pathophysiology of WC. LEVEL OF EVIDENCE: 2c.
[Mh] Termos MeSH primário: Toxinas Botulínicas/uso terapêutico
Distúrbios Distônicos/tratamento farmacológico
Amplitude de Movimento Articular/fisiologia
[Mh] Termos MeSH secundário: Adulto
Fatores Etários
Estudos de Casos e Controles
Distúrbios Distônicos/diagnóstico
Distúrbios Distônicos/reabilitação
Articulação do Cotovelo/fisiopatologia
Feminino
Articulações dos Dedos/efeitos dos fármacos
Articulações dos Dedos/fisiopatologia
Seres Humanos
Injeções Intralesionais
Masculino
Meia-Idade
Amplitude de Movimento Articular/efeitos dos fármacos
Valores de Referência
Medição de Risco
Índice de Gravidade de Doença
Fatores Sexuais
Resultado do Tratamento
Articulação do Punho/fisiopatologia
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
EC 3.4.24.69 (Botulinum Toxins)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171128
[Lr] Data última revisão:
171128
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE


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[PMID]:29064979
[Au] Autor:Solish N
[Ad] Endereço:Dermatology, University of Toronto, Toronto, Ontario, Canada.
[Ti] Título:Commentary on Aesthetic Treatment With Botulinum Toxin.
[So] Source:Dermatol Surg;43 Suppl 2:S157, 2017 11.
[Is] ISSN:1524-4725
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Toxinas Botulínicas
Fármacos Neuromusculares
[Mh] Termos MeSH secundário: Toxinas Botulínicas Tipo A
Estética
Seres Humanos
Envelhecimento da Pele
[Pt] Tipo de publicação:JOURNAL ARTICLE; COMMENT
[Nm] Nome de substância:
0 (Neuromuscular Agents); EC 3.4.24.69 (Botulinum Toxins); EC 3.4.24.69 (Botulinum Toxins, Type A)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171106
[Lr] Data última revisão:
171106
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171025
[St] Status:MEDLINE
[do] DOI:10.1097/DSS.0000000000001371


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[PMID]:28889761
[Au] Autor:Araklitis G; Cardozo L
[Ad] Endereço:a Department of Urogynaecology , King's College Hospital , London , UK.
[Ti] Título:Safety issues associated with using medication to treat overactive bladder.
[So] Source:Expert Opin Drug Saf;16(11):1273-1280, 2017 Nov.
[Is] ISSN:1744-764X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: The mainstay of overactive bladder treatment is the use of anticholinergic medication with its common side effects well known. This review focused on three less well-known safety issues when treating OAB. Areas covered: Patients with increased anticholinergic load are at risk of cognitive decline, dementia or even death. The elderly are particularly at risk due to polypharmacy. Botulinum toxin carries the risk of high urinary residuals, urinary tract infection and need to self catheterise. The use of vaginal oestrogens may improve OAB symptoms, but there is concern in those with a history of breast cancer. Studies have shown that the systemic absorption is negligible and does not increase the risk of recurrence. Expert Opinion: Improvement in assessing anticholinergic load is needed with the development of a universal drug scale. To avoid increasing load, Mirabegron or botulinum toxin can be used instead. There is no consensus of the use of prophylactic antibiotics when injecting botulinum toxin and at what residual to initiate self catheterisation. Despite evidence showing that the use of vaginal oestrogens is safe in those with a history of cancer, it is not fully supported by any health body. Further work is needed in those using aromatase inhibitors.
[Mh] Termos MeSH primário: Antagonistas Colinérgicos/efeitos adversos
Bexiga Urinária Hiperativa/tratamento farmacológico
Agentes Urológicos/efeitos adversos
[Mh] Termos MeSH secundário: Acetanilidas/administração & dosagem
Acetanilidas/efeitos adversos
Idoso
Toxinas Botulínicas/administração & dosagem
Toxinas Botulínicas/efeitos adversos
Antagonistas Colinérgicos/administração & dosagem
Estrogênios/administração & dosagem
Estrogênios/efeitos adversos
Seres Humanos
Polimedicação
Tiazóis/administração & dosagem
Tiazóis/efeitos adversos
Agentes Urológicos/administração & dosagem
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Acetanilides); 0 (Cholinergic Antagonists); 0 (Estrogens); 0 (Thiazoles); 0 (Urological Agents); EC 3.4.24.69 (Botulinum Toxins); MVR3JL3B2V (mirabegron)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170912
[St] Status:MEDLINE
[do] DOI:10.1080/14740338.2017.1376646


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[PMID]:28882889
[Au] Autor:Rohrbeck A; Höltje M; Adolf A; Oms E; Hagemann S; Ahnert-Hilger G; Just I
[Ad] Endereço:From the Institute of Toxicology, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover and rohrbeck.astrid@mh-hannover.de.
[Ti] Título:The Rho ADP-ribosylating C3 exoenzyme binds cells via an Arg-Gly-Asp motif.
[So] Source:J Biol Chem;292(43):17668-17680, 2017 Oct 27.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The Rho ADP-ribosylating C3 exoenzyme (C3bot) is a bacterial protein toxin devoid of a cell-binding or -translocation domain. Nevertheless, C3 can efficiently enter intact cells, including neurons, but the mechanism of C3 binding and uptake is not yet understood. Previously, we identified the intermediate filament vimentin as an extracellular membranous interaction partner of C3. However, uptake of C3 into cells still occurs (although reduced) in the absence of vimentin, indicating involvement of an additional host cell receptor. C3 harbors an Arg-Gly-Asp (RGD) motif, which is the major integrin-binding site, present in a variety of integrin ligands. To check whether the RGD motif of C3 is involved in binding to cells, we performed a competition assay with C3 and RGD peptide or with a monoclonal antibody binding to ß1-integrin subunit and binding assays in different cell lines, primary neurons, and synaptosomes with C3-RGD mutants. Here, we report that preincubation of cells with the GRGDNP peptide strongly reduced C3 binding to cells. Moreover, mutation of the RGD motif reduced C3 binding to intact cells and also to recombinant vimentin. Anti-integrin antibodies also lowered the C3 binding to cells. Our results indicate that the RGD motif of C3 is at least one essential C3 motif for binding to host cells and that integrin is an additional receptor for C3 besides vimentin.
[Mh] Termos MeSH primário: ADP Ribose Transferases
Toxinas Botulínicas
Integrina beta1
Neurônios/metabolismo
Oligopeptídeos
Sinaptossomos/metabolismo
[Mh] Termos MeSH secundário: ADP Ribose Transferases/química
ADP Ribose Transferases/farmacocinética
ADP Ribose Transferases/farmacologia
Motivos de Aminoácidos
Animais
Toxinas Botulínicas/química
Toxinas Botulínicas/farmacocinética
Toxinas Botulínicas/farmacologia
Linhagem Celular
Integrina beta1/química
Integrina beta1/genética
Integrina beta1/metabolismo
Camundongos
Vimentina/química
Vimentina/genética
Vimentina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Integrin beta1); 0 (Oligopeptides); 0 (Vimentin); 78VO7F77PN (arginyl-glycyl-aspartic acid); EC 2.4.2.- (ADP Ribose Transferases); EC 2.4.2.- (exoenzyme C3, Clostridium botulinum); EC 3.4.24.69 (Botulinum Toxins)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170909
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.798231



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