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Archives of Biochemistry and Biophysics Jan 2021Human flavin-containing monooxygenase 3 (FMO3) is a membrane-bound, phase I drug metabolizing enzyme. It is highly polymorphic with some of its variants demonstrating...
Human flavin-containing monooxygenase 3 (FMO3) is a membrane-bound, phase I drug metabolizing enzyme. It is highly polymorphic with some of its variants demonstrating differences in rates of turnover of its substrates: xenobiotics including drugs as well as dietary compounds. In order to measure its in vitro activity and compare any differences between the wild type enzyme and its polymorphic variants, we undertook a systematic study using different engineered proteins, heterologously expressed in bacteria, purified and catalytically characterized with 3 different substrates. These included the full-length as well as the more soluble C-terminal truncated versions of the common polymorphic variants (E158K, V257M and E308G) of FMO3 in addition to the full-length and truncated wild-type proteins. In vitro activity assays were performed with benzydamine, tamoxifen and sulindac sulfide, whose products were measured by HPLC. Differences in catalytic properties between the wild-type FMO3 and its common polymorphic variants were similar to those observed with the truncated, more soluble versions of the enzymes. Interestingly, the truncated enzymes were better catalysts than the full-length proteins. The data obtained point to the feasibility of using the more soluble forms of this enzyme for in vitro drug assays as well as future biotechnological applications possibly in high throughput systems such as bioelectrochemical platforms and biosensors.
Topics: Humans; Models, Molecular; Oxidation-Reduction; Oxygen; Oxygenases; Polymorphism, Genetic; Protein Conformation
PubMed: 33152328
DOI: 10.1016/j.abb.2020.108663 -
The Cochrane Database of Systematic... Aug 2010Treatment of cancer is increasingly effective but associated with short and long term side effects. Oral side effects, including oral mucositis (mouth ulceration),... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Treatment of cancer is increasingly effective but associated with short and long term side effects. Oral side effects, including oral mucositis (mouth ulceration), remain a major source of illness despite the use of a variety of agents to treat them.
OBJECTIVES
To assess the effectiveness of interventions for treating oral mucositis or its associated pain in patients with cancer receiving chemotherapy or radiotherapy or both.
SEARCH STRATEGY
Electronic searches of Cochrane Oral Health Group and PaPaS Trials Registers (to 1 June 2010), CENTRAL via The Cochrane Library (to Issue 2, 2010), MEDLINE via OVID (1950 to 1 June 2010), EMBASE via OVID (1980 to 1 June 2010), CINAHL via EBSCO (1980 to 1 June 2010), CANCERLIT via PubMed (1950 to 1 June 2010), OpenSIGLE (1980 to 1 June 2010) and LILACS via the Virtual Health Library (1980 to 1 June 2010) were undertaken. Reference lists from relevant articles were searched and the authors of eligible trials were contacted to identify trials and obtain additional information.
SELECTION CRITERIA
All randomised controlled trials comparing agents prescribed to treat oral mucositis in people receiving chemotherapy or radiotherapy or both. Outcomes were oral mucositis, time to heal mucositis, oral pain, duration of pain control, dysphagia, systemic infection, amount of analgesia, length of hospitalisation, cost and quality of life.
DATA COLLECTION AND ANALYSIS
Data were independently extracted, in duplicate, by two review authors. Authors were contacted for details of randomisation, blindness and withdrawals. Risk of bias assessment was carried out on six domains. The Cochrane Collaboration statistical guidelines were followed and risk ratio (RR) values calculated using fixed-effect models (less than 3 trials in each meta-analysis).
MAIN RESULTS
Thirty-two trials involving 1505 patients satisfied the inclusion criteria. Three comparisons for mucositis treatment including two or more trials were: benzydamine HCl versus placebo, sucralfate versus placebo and low level laser versus sham procedure. Only the low level laser showed a reduction in severe mucositis when compared with the sham procedure, RR 5.28 (95% confidence interval (CI) 2.30 to 12.13).Only 3 comparisons included more than one trial for pain control: patient controlled analgesia (PCA) compared to the continuous infusion method, therapist versus control, cognitive behaviour therapy versus control. There was no evidence of a difference in mean pain score between PCA and continuous infusion, however, less opiate was used per hour for PCA, mean difference 0.65 mg/hour (95% CI 0.09 to 1.20), and the duration of pain was less 1.9 days (95% CI 0.3 to 3.5).
AUTHORS' CONCLUSIONS
There is weak and unreliable evidence that low level laser treatment reduces the severity of the mucositis. Less opiate is used for PCA versus continuous infusion. Further, well designed, placebo or no treatment controlled trials assessing the effectiveness of interventions investigated in this review and new interventions for treating mucositis are needed.
Topics: Analgesics; Anti-Ulcer Agents; Humans; Low-Level Light Therapy; Mouth Diseases; Neoplasms; Oral Ulcer; Pain; Pain Management; Randomized Controlled Trials as Topic; Stomatitis
PubMed: 20687070
DOI: 10.1002/14651858.CD001973.pub4 -
International Journal of Medical... 2013Oral rinses are widely used to promote periodontal health with provisional restorations during the interim period. The aim of this study was to compare the discoloration...
PURPOSE
Oral rinses are widely used to promote periodontal health with provisional restorations during the interim period. The aim of this study was to compare the discoloration of provisional restoration materials with different oral rinses.
MATERIAL AND METHODS
A total of 140 disc-shaped specimens (shade A2) (10 mm x 2 mm) were prepared from one PMMA-based (TemDent Classic(®)) and three different bis-acrylic-based (Protemp II(®), Luxatemp(®) and Fill-In(®)) provisional restoration materials (n=7). The color values (L*, a*, and b*) of each specimen were measured before and after exposure with a colorimeter, and the color changes (∆E) were calculated according to the CIE L*a*b* system. The specimens were immersed in each of the 4 oral rinses (alcohol-containing mouthwash, chlorhexidine, benzydamine HCl, benzydamine HCl and chlorhexidine) twice a day for 2 minutes. After 2 minutes of immersion in the oral rinses, the specimens were immersed in artificial saliva. The specimens were exposed to the oral rinses and the artificial saliva for 3 weeks. Two-way ANOVA, the Bonferroni test and the paired sample t-test were used for statistical analyses (p<0.05).
RESULTS
Comparison of the discoloration from the oral rinses after immersion for three weeks revealed no significant differences (p>0.05). The lowest color change was observed in PMMA-based Temdent in all oral rinses (p<0.05). There were no significant differences between the bis-acryl composites after immersion in saliva or the mixture of benzydamine HCl and chlorhexidine and the alcohol-containing mouthwash for 3 weeks (p>0.05). After immersion in chlorhexidine, the color change values of Protemp II and Fill-in showed significant differences (p=0.018). Protemp II also showed less discoloration than the other bis-acryl composites, and this color change was statistically significant (p <0.05). For all oral rinses, the L* value decreased while b* values increased, and this color change was found to be statistically significant (p <0.05). A* values were found to be significantly higher with oral rinses (p<0.05), except Protemp II immersed in benzydamine HCl or alcohol-containing mouthwash.
CONCLUSIONS
The type of the oral rinse did not affect the discoloration process. For long-term esthetic results, choosing MMA-based materials for provisional restorations appears to be more effective.
Topics: Benzydamine; Chlorhexidine; Humans; Mouthwashes; Saliva
PubMed: 24046524
DOI: 10.7150/ijms.6647 -
Ciencia & Saude Coletiva May 2010The abusive drug use has been object of increasing concern in public health and is commonly issued in the Brazilian press. Amongst medicines, those that are abuse... (Review)
Review
The abusive drug use has been object of increasing concern in public health and is commonly issued in the Brazilian press. Amongst medicines, those that are abuse substances and cause physical and/or psychic dependence, barbiturates, benzodiazepines, opioid analgesics and amphetamines are included. Analgesics, antipyretics and non-steroidal anti-inflammatory drugs, even not making part of this list, are generally associated with recreational use or non therapeutical purpose. The objective of this essay is to present information on the abusive use of benzydamine in Brazil. The present study is an exploratory essay in which different methodological strategies adopted in the regulatory practice of pharmacovigilance have been used. The abusive use of this drug was evidenced in scientific literature, press releases and on the internet. Considering the facility of purchasing drugs under medical prescription, among other factors, it must be demanded ways to assess the marketing and use of medicines, and assure its safe and rational use, including the strengthening of pharmacovigilance in Brazil.
Topics: Adverse Drug Reaction Reporting Systems; Benzydamine; Brazil; Humans; Substance-Related Disorders
PubMed: 20464184
DOI: 10.1590/s1413-81232010000300014 -
Pharmaceutics Jul 2023This study aims to design a novel thiolated κ-carrageenan (κ-CA-SH) and evaluate its potential as an excipient for the design of mucoadhesive drug delivery systems.
AIM
This study aims to design a novel thiolated κ-carrageenan (κ-CA-SH) and evaluate its potential as an excipient for the design of mucoadhesive drug delivery systems.
METHODS
Native κ-carrageenan (κ-CA) was thiolated with phosphorous pentasulfide in sulfolane and characterized via H NMR, FTIR, as well as Ellman's test. Cytotoxicity was assessed via resazurin assay. In vitro release of the model drug, benzydamine hydrochloride, was determined. Tensile and mucosal residence time studies were performed on buccal and small intestinal mucosa. Mucoadhesive features were investigated via rheological studies with freshly isolated porcine mucus.
RESULTS
Thiolated κ-CA (κ-CA-SH) with 1213.88 ± 52 µmol/g thiol groups showed no cytotoxicity at a concentration of 1% (/) and low cytotoxicity up to 2% (/). Benzydamine hydrochloride showed slow release in solution for both polymers. Tensile studies on buccal and intestinal mucosa showed an up to 2.7-fold and 7.7-fold enhancement in the maximum detachment force (MDF) and total work of adhesion (TWA) of κ-CA-SH vs. κ-CA, respectively. The κ-CA-SH exhibited an up to 4.4-fold improved dynamic viscosity with mucus and significantly prolonged residence time on mucosa compared to native κ-CA.
CONCLUSION
Since highly thiolated κ-CA shows a slow release of positively charged active pharmaceutical ingredients and enhanced mucoadhesive properties, it might be a promising excipient for local drug delivery in the oral cavity.
PubMed: 37514179
DOI: 10.3390/pharmaceutics15071993 -
Minerva Anestesiologica Jan 2019Sore throat and hoarseness are common complications after surgery. Flurbiprofen spray has been successfully used for treatment of oral inflammations, but its effects on... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Sore throat and hoarseness are common complications after surgery. Flurbiprofen spray has been successfully used for treatment of oral inflammations, but its effects on postoperative sore throat and hoarseness are unknown. We conducted this study to evaluate the effectiveness of flurbiprofen spray on postoperative sore throat and hoarseness, by comparing it with benzydamine hydrochloride spray and placebo.
METHODS
One hundred fifty patients who were scheduled to undergo elective ear surgery were enrolled. Patients were randomized to three groups of 50 patients each; flurbiprofen oral spray, benzydamine hydrochloride oral spray and placebo spray groups. Patients received sprays just before intubation, and the incidence and severity of postoperative sore throat and hoarseness were evaluated by a blinded investigator at 0, 1, 6 and 24-hour post extubation. Patients were also questioned for possible side effects at all time points.
RESULTS
The sore throat severity scores were significantly lower in treatment groups when compared to placebo group at all time points (P=0.003/108). Similarly, the incidence of sore throat was significantly lower in both of the treatment groups (P=0.007/104). The incidence of hoarseness and hoarseness scores were significantly lower in treatment groups when compared to placebo group (P=0.006/105 and P=0.005/104, respectively). While none of the patients complained of any adverse effects in flurbiprofen group, only two patients in benzydamine hydrochloride group experienced numbness.
CONCLUSIONS
Both oral flurbiprofen and benzydamine hydrochloride sprays were found to be more effective than placebo in decreasing the incidence and severity of postoperative sore throat and hoarseness, with no adverse effects.
Topics: Adolescent; Adult; Aerosols; Anti-Inflammatory Agents, Non-Steroidal; Benzydamine; Double-Blind Method; Ear; Female; Flurbiprofen; Hoarseness; Humans; Incidence; Male; Middle Aged; Pharyngitis; Postoperative Complications; Prospective Studies; Young Adult
PubMed: 29756749
DOI: 10.23736/S0375-9393.18.12703-9 -
British Journal of Clinical Pharmacology Oct 2000AIMS To determine the FMO and P450 isoform selectivity for metabolism of benzydamine and caffeine, two potential in vivo probes for human FMO. METHODS Metabolic...
UNLABELLED
AIMS To determine the FMO and P450 isoform selectivity for metabolism of benzydamine and caffeine, two potential in vivo probes for human FMO. METHODS Metabolic incubations were conducted at physiological pH using substrate concentrations of 0.01-10 mM with either recombinant human FMOs, P450s or human liver microsomes serving as the enzyme source. Products of caffeine and benzydamine metabolism were analysed by reversed-phase h.p.l.c. with u.v. and fluorescence detection. RESULTS CYP1A2, but none of the human FMOs, catalysed metabolism of caffeine. In contrast, benzydamine was a substrate for human FMO1, FMO3, FMO4 and FMO5. Apparent Km values for benzydamine N-oxygenation were 60 +/- 8 microM, 80 +/- 8 microM, > 3 mM and > 2 mM, for FMO1, FMO3, FMO4 and FMO5, respectively. The corresponding Vmax values were 46 +/- 2 min-1, 36 +/- 2 min-1, < 75 min-1 and < 1 min-1. Small quantities of benzydamine N-oxide were also formed by CYPs 1A1, 1A2, 2C19, 2D6 and 3A4.
CONCLUSIONS
FMO1 and FMO3 catalyse benzydamine N-oxygenation with the highest efficiency. However, it is likely that the metabolic capacity of hepatic FMO3 is a much greater contributor to plasma levels of the N-oxide metabolite in vivo than is extrahepatic FMO1. Therefore, benzydamine, but not caffeine, is a potential in vivo probe for human FMO3.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Benzydamine; Caffeine; Chromatography, High Pressure Liquid; Cytochrome P-450 Enzyme System; Humans; Isoenzymes; Microsomes, Liver; Oxidation-Reduction; Oxygenases
PubMed: 11012553
DOI: 10.1046/j.1365-2125.2000.00265.x -
ISRN Obstetrics and Gynecology 2012Two hundred and 91 patients showing signs and symptoms of bacterial vaginosis (BV) were randomized to receive topical treatment with Fitostimoline (vaginal cream and...
Efficacy and tolerability of fitostimoline (vaginal cream, ovules, and vaginal washing) and of benzydamine hydrochloride (tantum rosa vaginal cream and vaginal washing) in the topical treatment of symptoms of bacterial vaginosis.
Two hundred and 91 patients showing signs and symptoms of bacterial vaginosis (BV) were randomized to receive topical treatment with Fitostimoline (vaginal cream and vaginal ovules + vaginal washing) or benzydamine hydrochloride (vaginal cream + vaginal washing) for 7 days. Signs (leucorrhoea, erythema, oedema, and erosion) and symptoms (burning, pain, itching, vaginal dryness, dyspareunia, and dysuria) (scored 0-3) were evaluated at baseline and at the end of treatment; the total symptoms score (TSS) was also calculated. In 125 patients, a bacterial vaginosis was confirmed by vaginal swab test. The primary efficacy variable analysis, that is, the percentage of patients with therapeutic success (almost complete disappearance of signs and symptoms), demonstrated that Fitostimoline ovules and vaginal cream were therapeutically equivalent and that pooled Fitostimoline treatment was not inferior to benzydamine hydrochloride. All the treatments were well tolerated, with only minor local adverse events infrequently reported. The results of this study confirmed that gynaecological Fitostimoline is a safe and effective topical treatment for BV.
PubMed: 23209922
DOI: 10.5402/2012/183403 -
Cureus Feb 2024Postoperative sore throat (POST) is the most common discomfort after endotracheal intubation. Damage to the tracheal mucosa caused by inappropriate endotracheal tube...
OBJECTIVE
Postoperative sore throat (POST) is the most common discomfort after endotracheal intubation. Damage to the tracheal mucosa caused by inappropriate endotracheal tube (ETT) cuff pressure has been shown as the major factor. Monitoring the ETT cuff pressure at a certain value reduces this damage. Benzydamine hydrochloride (BH) has proven to be effective on sore throat and studies have shown that it is also effective on POST. In this study, the efficacy of BH and ETT cuff pressure monitoring on POST was evaluated.
MATERIALS AND METHODS
After ethics committee approval 210 patients in the ASA (American Society of Anesthesiologists) I-III risk group undergoing elective surgery were included in the study. Routine anesthesia monitoring, induction, and maintenance were provided. Patients were randomly divided into three groups. Thirty minutes before surgery, the posterior pharyngeal wall was sprayed with BH in group 1 and distilled water in groups 2 and 3. Intraoperatively, the first and second groups were monitored to keep the ETT cuff pressure between 22 and 26 cmHO, while no intervention was performed in the third group. The incidence and severity of postoperative dysphagia, hoarseness, and POST were questioned.
RESULTS
There was no difference between demographic data, and gender was not associated with POST. There was a statistically significant difference between the first and second groups and the third group in terms of all three symptoms questioned (p<0.01). No difference was observed between the first and second groups. Side effect rates were similar. Smoking was not found to be associated with symptoms.
CONCLUSION
The incidence and severity of POST, dysphagia, and hoarseness are reduced when the ETT cuff is inflated with a pressure of 22-26 cmHO after intubation with a manometer and maintained at this pressure range throughout the operation. There was no beneficial effect of BH.
PubMed: 38322097
DOI: 10.7759/cureus.53725 -
British Medical Journal (Clinical... May 1988
Topics: Benzydamine; Drug Eruptions; Humans; Mouthwashes; Pyrazoles
PubMed: 2969272
DOI: 10.1136/bmj.296.6633.1402-f