Botulinum toxin and its clinical applications

Botulin, exotoxin produced by C. botulinum, is one of the most potent toxins known to the mankind. For nearly 40 years it has been successfully used in various fields of medicine, despite the word botox is still mainly associated with aesthetic medicine and more or less successful beauty treatments. The review of the literature and description of the current knowledge about botulinum toxin and its clinical applications was the aim of the study. Botulinum toxin is protein composed of two chains linked together by a disulfide bridge. Seven serotypes were distinguish and label from A to G. The botulinum toxin mechanism of action involves proteolysis of specific neuronal proteins which resulting in blockade of acetylcholine release from presynaptic vesicles at the neuromuscular junction. For the first time botulin was used by A. Scott in treatment of strabismus. Since then botulinum neurotoxin has found its application in such areas as ophthalmology, neurology and urology. Botulinum proved to be a safe drug with few adverse effects, among which dysphagia is the most dangerous. Although the effect of botulinum toxin is unstable and reversible, there is a possibility of appearance of antibodies and clinical resistance, particularly in patients undergoing long-term therapy. Since the discovery, botulinum neurotoxin, has undergone a transformation from the deadly poison to the drug used in many areas of medicine. Numerous studies confirm that botulin, when used responsibly with the smallest effective dose and required intervals, is safe for the organism. Botulin can be for physicians a therapeutic tool, which can bring relief from the symptoms and suffering and significantly improving patients quality of life.

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Long‐term therapy with botulinum toxin in facial synkinesis: Retrospective data analysis of data from 1998 to 2018

Clinical Otolaryngology ◽

10.1111/coa.13729 ◽

2021 ◽

Author(s):

Sara Alipour ◽

Carina Pick ◽

Stefanie Jansen ◽

Svenja Rink ◽

Jens Peter Klußmann ◽

...

Keyword(s):

Data Analysis ◽

Botulinum Toxin ◽

Term Therapy ◽

Retrospective Data ◽

Retrospective Data Analysis ◽

Long Term Therapy ◽

Facial Synkinesis

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New trends in botulinum toxin use in dermatology

Dermatology Practical & Conceptual ◽

10.5826/dpc.0804a05 ◽

2018 ◽

pp. 277-282 ◽

Cited By ~ 4

Author(s):

Stefania Guida ◽

Francesca Farnetani ◽

Steven P. Nisticò ◽

Caterina Giorgio Mariarosaria ◽

Graziella Babino ◽

...

Keyword(s):

Botulinum Toxin ◽

Botulinum Neurotoxin ◽

Current Knowledge ◽

Hypertrophic Scars ◽

Skin Disorders ◽

Facial Flushing ◽

Cutaneous Lesions ◽

Raynaud Phenomenon ◽

Skin Conditions ◽

Review Current

Background: Recent studies have highlighted new botulinum neurotoxin (BoNT) applications in the field of dermatology. Objective: To review current knowledge of BoNT use in dermatology. Methods: The literature of the last 5 years has been reviewed. Results: We describe interesting protocols of BoNT treatment for hyperhidrosis (HH), hypertrophic scars and keloids, Raynaud phenomenon, facial flushing, oily skin, psoriasis, Hailey-Hailey disease, and cutaneous lesions like painful lesions and periorbital syringomas. Conclusions: Several skin conditions eligible for BoNT treatment have been described. After the wide application for HH treatment, scars as well as vascular and inflammatory skin disorders, oily skin and cutaneous lesions represent fields of application of BoNT.

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Emergence and Evolution of Enfuvirtide Resistance following Long-Term Therapy Involves Heptad Repeat 2 Mutations within gp41

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.49.3.1113-1119.2005 ◽

2005 ◽

Vol 49 (3) ◽

pp. 1113-1119 ◽

Cited By ~ 128

Author(s):

L. Xu ◽

A. Pozniak ◽

A. Wildfire ◽

S. A. Stanfield-Oakley ◽

S. M. Mosier ◽

...

Keyword(s):

Amino Acids ◽

Heptad Repeat ◽

Term Therapy ◽

Compensatory Mutation ◽

Two Samples ◽

Close Proximity ◽

Long Term Therapy ◽

Changes Over Time ◽

First Time

ABSTRACT The objective of this study was to track the evolution of sequence changes in both the heptad region 1 (HR1) and HR2 domains of gp41 associated with resistance to enfuvirtide (ENF) in a patient cohort receiving long-term ENF treatment. We studied 17 highly antiretroviral agent-experienced patients receiving long-term ENF treatment with virological rebound or a lack of suppression. Sixty-two samples obtained after between 5 and 107 weeks of ENF therapy were analyzed. Baseline samples from 15 of these 17 patients were available for analysis. Viruses from five samples from four patients were also sequenced after the cessation of ENF therapy. Drug susceptibilities were assessed by a pseudotype virus reporter assay. We identified HR1 and HR2 sequence changes over time in relation to the baseline sequences. Mutations in HR1 (amino acids 36 to 45) were noted in all cases, including previously unreported changes N42Q/H and N43Q. In addition to a range of HR2 sequence changes at polymorphic sites, isolates from 6 of 17 (35%) patients developed an S138A substitution in the HR2 domain at least 8 weeks after the start of ENF treatment and also subsequent to the first emergence of HR1 mutations. In most, but not all, cases the S138A mutation accompanied HR1 mutations at position 43. Molecular modeling demonstrates the close proximity of S138A with amino acids 40 and 45 in HR1. Of note, isolates in samples available from four patients demonstrated the loss of both the HR1 and the S138A HR2 mutations following the cessation of therapy. We show that the S138A HR2 mutation increased the level of resistance by approximately threefold over that conferred by the HR1 mutation N43D. Continual evolution of HR1 in the domain from amino acids 36 to 45 was observed during long-term ENF therapy. We have identified, for the first time, an ENF resistance-associated HR2 mutation, S138A, which appeared in isolates from 6 of 17 patients with virological failure and demonstrated its potential to contribute to drug resistance. We propose that this represents a possible secondary and/or compensatory mutation, particularly when it coexists with mutations at position 43 in HR-1.

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Botulinum Toxin in Long-Term Therapy for Achalasia

Annals of Internal Medicine ◽

10.7326/0003-4819-128-8-199804150-00026 ◽

1998 ◽

Vol 128 (8) ◽

pp. 696 ◽

Cited By ~ 13

Author(s):

Vito Annese

Keyword(s):

Botulinum Toxin ◽

Term Therapy ◽

Long Term Therapy

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Amoxycillin and Clavulanic Acid in the Treatment of Urinary Tract Infections in Children

Journal of International Medical Research ◽

10.1177/030006058901700209 ◽

1989 ◽

Vol 17 (2) ◽

pp. 168-171 ◽

Cited By ~ 4

Author(s):

U. Ruberto ◽

P. D'Eufemia ◽

F. Martino ◽

O. Giardini

Keyword(s):

Urinary Tract ◽

Clavulanic Acid ◽

Urinary Tract Infections ◽

Term Therapy ◽

First Choice ◽

Amoxicillin Clavulanic Acid ◽

Tract Infections ◽

Long Term Therapy ◽

First Time

The efficacy of amoxicillin–clavulanic acid combination in the treatment of urinary tract infections resistant, in vitro, to amoxycillin was studied in 42 children. Of the 24 children with urinary tract infection for the first time, combination therapy, dosing twice daily for 5 days (40 mg/kg·day), cleared the infection in 23 (96%) cases. Relapse occurred in four (17%) cases within 30 days. Of the 18 children who presented with recurrent urinary tract infections therapy, as above, cleared the infection in 16 (89%) cases. In these cases, long-term therapy was performed at a dosage of 20 mg/kg once daily. Tolerance was good; gastro-intestinal disorders in five (12%) cases which regressed by dosing at 8 h rather than 12 h intervals. In conclusion, amoxycillin–clavulanic acid can be considered a first choice treatment of urinary tract infections in children.

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New trends in botulinum toxin use in dermatology

Dermatology Practical & Conceptual ◽

10.5826/10.5826/dpc.0804a05 ◽

2019 ◽

pp. 277-282

Author(s):

Stefania Guida ◽

Francesca Farnetani ◽

Steven Nisticò ◽

Caterina Giorgio Mariarosaria ◽

Graziella Babino ◽

...

Keyword(s):

Botulinum Toxin ◽

Botulinum Neurotoxin ◽

Current Knowledge ◽

Hypertrophic Scars ◽

Skin Disorders ◽

Facial Flushing ◽

Cutaneous Lesions ◽

Raynaud Phenomenon ◽

Skin Conditions ◽

Review Current

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Cellular Cullin RING Ubiquitin Ligases: Druggable Host Dependency Factors of Cytomegaloviruses

International Journal of Molecular Sciences ◽

10.3390/ijms20071636 ◽

2019 ◽

Vol 20 (7) ◽

pp. 1636 ◽

Cited By ~ 11

Author(s):

Tanja Becker ◽

Vu Le-Trilling ◽

Mirko Trilling

Keyword(s):

Drug Targets ◽

Current Knowledge ◽

Antiviral Treatment ◽

Term Therapy ◽

Restriction Factors ◽

Intrinsic Immunity ◽

Host Restriction ◽

Host Restriction Factors ◽

Inhibitory Compound ◽

Long Term Therapy

Human cytomegalovirus (HCMV) is a ubiquitous betaherpesvirus that frequently causes morbidity and mortality in individuals with insufficient immunity, such as transplant recipients, AIDS patients, and congenitally infected newborns. Several antiviral drugs are approved to treat HCMV infections. However, resistant HCMV mutants can arise in patients receiving long-term therapy. Additionally, side effects and the risk to cause birth defects limit the use of currently approved antivirals against HCMV. Therefore, the identification of new drug targets is of clinical relevance. Recent work identified DNA-damage binding protein 1 (DDB1) and the family of the cellular cullin (Cul) RING ubiquitin (Ub) ligases (CRLs) as host-derived factors that are relevant for the replication of human and mouse cytomegaloviruses. The first-in-class CRL inhibitory compound Pevonedistat (also called MLN4924) is currently under investigation as an anti-tumor drug in several clinical trials. Cytomegaloviruses exploit CRLs to regulate the abundance of viral proteins, and to induce the proteasomal degradation of host restriction factors involved in innate and intrinsic immunity. Accordingly, pharmacological blockade of CRL activity diminishes viral replication in cell culture. In this review, we summarize the current knowledge concerning the relevance of DDB1 and CRLs during cytomegalovirus replication and discuss chances and drawbacks of CRL inhibitory drugs as potential antiviral treatment against HCMV.

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Long-term therapy of benign essential blepharospasm and facial hemispasm with botulinum toxin A: retrospective assessment of the clinical and quality of life impact in patients treated for more than 15 years

Acta Neurologica Belgica ◽

10.1007/s13760-014-0285-z ◽

2014 ◽

Vol 114 (4) ◽

pp. 285-291 ◽

Cited By ~ 19

Author(s):

Hana Streitová ◽

Martin Bareš

Keyword(s):

Quality Of Life ◽

Botulinum Toxin ◽

Botulinum Toxin A ◽

Term Therapy ◽

Retrospective Assessment ◽

Essential Blepharospasm ◽

Life Impact ◽

Long Term Therapy

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Neuro-Oncology Practice Clinical Debate: long-term antiepileptic drug prophylaxis in patients with glioma

Neuro-Oncology Practice ◽

10.1093/nop/npaa026 ◽

2020 ◽

Vol 7 (6) ◽

pp. 583-588

Author(s):

Brian Stocksdale ◽

Seema Nagpal ◽

John D Hixson ◽

Derek R Johnson ◽

Prashant Rai ◽

...

Keyword(s):

Standard Of Care ◽

Term Therapy ◽

Tumor Patients ◽

Oncology Practice ◽

Long Term Therapy ◽

First Time ◽

Drug Prophylaxis

Abstract Patients with primary brain tumors often experience seizures, which can be the presenting symptom or occur for the first time at any point along the illness trajectory. In addition to causing morbidity, seizures negatively affect independence and quality of life in other ways, for example, by leading to loss of driving privileges. Long-term therapy with antiepileptic drugs (AEDs) is the standard of care in brain tumor patients with seizures, but the role of prophylactic AEDs in seizure-naive patients remains controversial. In this article, experts in the field discuss the issues of AED efficacy and toxicity, and explain their differing recommendations for routine use of prophylactic AEDs.

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