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PubMed2004

Combinations of topical fluoride (toothpastes, mouthrinses, gels, varnishes) versus single topical fluoride for preventing dental caries in children and adolescents.

BACKGROUND: Topical fluoride therapy (TFT) in the form of toothpastes, mouthrinses, varnishes and gels are effective caries preventive measures. However, there is uncertainty about the relative value of these interventions when used together. OBJECTIVES: To compare the effectiveness of two TFT modalities combined with one of them alone (mainly toothpaste) when used for the prevention of dental caries in children. SEARCH STRATEGY: We searched the Cochrane Oral Health Group's Trials Register (May 2000), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2000), MEDLINE (1966 to January 2000), plus several other databases. We handsearched journals, reference lists of articles and contacted selected authors and manufacturers. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials with blind outcome assessment, comparing fluoride varnish, gel, mouthrinse, or toothpaste in combination with each other in children up to 16 years during at least 1 year. The main outcome was caries increment measured by the change in decayed, missing and filled tooth surfaces (D(M)FS). DATA COLLECTION AND ANALYSIS: Inclusion decisions, quality assessment and data extraction were duplicated in a random sample of one third of studies, and consensus achieved by discussion or a third party. Authors were contacted for missing data. The primary measure of effect was the prevented fraction (PF) that is the difference in mean caries increments between the 'treatment' and 'control' groups expressed as a percentage of the mean increment in the control group. Random effects meta-analyses were performed where data could be pooled. MAIN RESULTS: Eleven of the 12 included studies contributed data for the meta-analyses. For the nine trials that provided data for the main meta-analysis on the effect of fluoride mouthrinses, gels or varnishes used in combination with toothpaste (involving 4026 children) the D(M)FS pooled PF was 10% (95% CI, 2% to 17%; p = 0.01) in favour of the combined regimens. Heterogeneity was not substantial in these results (I square = 32%). The separate meta-analyses of fluoride gel or mouthrinse combined with toothpaste versus toothpaste alone favour the combined regimens, but differences were not statistically significant; the significant difference in favour of the combined use of fluoride varnish and toothpaste accrues from a very small trial and appears likely to be a spurious result. Not all other combinations of possible practical value were tested in the included studies. The only other statistically significant result was in favour of the combined use of fluoride gel and mouthrinse in comparison to gel alone (pooled DMFS PF 23%; 95% CI, 4% to 43%; p = 0.02), based on two trials. No other combinations of TFT were consistently superior to a single TFT. REVIEWER'S CONCLUSIONS: Topical fluorides (mouthrinses, gels, or varnishes) used in addition to fluoride toothpaste achieve a modest reduction in caries compared to toothpaste used alone. No conclusions about any adverse effects could be reached, because data were scarcely reported in the trials.

Adolescent↗
PubMed2003

Topical fluoride (toothpastes, mouthrinses, gels or varnishes) for preventing dental caries in children and adolescents.

BACKGROUND: Topical fluoride therapy (TFT) in the form of varnish, gel, mouthrinse or toothpaste has been used extensively as a caries-preventive intervention for over three decades. OBJECTIVES: To determine the effectiveness and safety of fluoride varnishes, gels, mouthrinses, and toothpastes in the prevention of dental caries in children and to examine factors potentially modifying their effect. SEARCH STRATEGY: We searched the Cochrane Oral Health Group's Trials Register (May 2000), CENTRAL (The Cochrane Library Issue 2, 2000), MEDLINE (1966 to January 2000), plus several other databases. We handsearched journals, reference lists of articles and contacted selected authors and manufacturers. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials with blind outcome assessment, comparing fluoride varnish, gel, mouthrinse, or toothpaste with placebo or no treatment in children up to 16 years during at least 1 year. The main outcome was caries increment measured by the change in decayed, missing and filled tooth surfaces (D(M)FS). DATA COLLECTION AND ANALYSIS: Inclusion decisions, quality assessment and data extraction were duplicated in a random sample of one third of studies, and consensus achieved by discussion or a third party. Authors were contacted for missing data. The primary measure of effect was the prevented fraction (PF) that is the difference in mean caries increments between the treatment and control groups expressed as a percentage of the mean increment in the control group. Random effects meta-analyses were performed where data could be pooled. Potential sources of heterogeneity were examined in random effects metaregression analyses. MAIN RESULTS: There were 144 studies included. For the 133 that contributed data for meta-analysis (involving 65,169 children) the D(M)FS pooled prevented fraction estimate was 26% (95% CI, 24% to 29%; p < 0.0001). There was substantial heterogeneity, confirmed statistically (p < 0.0001), but the direction of effect was consistent. The effect of topical fluoride varied according to type of control group used, type of TFT used, mode/setting of TFT use, initial caries levels and intensity of TFT application, but was not influenced by exposure to water fluoridation or other fluoride sources. D(M)FS PF was on average 14% (95% CI, 5% to 23%; p = 0.002) higher in non-placebo controlled trials, 14% (95% CI, 2% to 26%; p = 0.25) higher in fluoride varnish trials compared with all others, and 10% (95% CI, -17% to -3%; p = 0.003) lower in trials of unsupervised home use compared with self applied supervised and operator-applied. There was a 0.7% increase in the PF per unit increase in baseline caries (95% CI, 0.2% to 1.2%; p = 0.004). REVIEWER'S CONCLUSIONS: The benefits of topical fluorides have been firmly established on a sizeable body of evidence from randomized controlled trials. While the formal examination of sources of heterogeneity between studies has been important in the overall conclusions reached, these should be interpreted with caution. We were unable to reach definite conclusions about any adverse effects that might result from the use of topical fluorides, because data reported in the trials are scarce.

Adolescent↗
PubMed2004

Fluorides for the prevention of white spots on teeth during fixed brace treatment.

BACKGROUND: White spots can appear on teeth during fixed brace treatment because of early decay around the brace attachments. Fluoride is effective at reducing decay in susceptible individuals and is routinely prescribed in various different forms to patients during orthodontic treatment. OBJECTIVES: To evaluate the effectiveness of fluoride in preventing white spots during orthodontic treatment and to compare the different modes of delivery of fluoride. SEARCH STRATEGY: We searched the Cochrane Oral Health Group's Trials Register (to 22 August 2002); CENTRAL (The Cochrane Library Issue 3, 2002); MEDLINE (January 1966 to July 2003); EMBASE (January 1980 to week July 2003). Authors of trials were contacted for further data. SELECTION CRITERIA: Trials were selected if they met the following criteria: a randomised or quasi-randomised clinical trial, involving the use of a fluoride-containing product compared with no use or use of a non-fluoride control and enamel demineralisation was assessed during or after orthodontic treatment. DATA COLLECTION AND ANALYSIS: Six reviewers independently, in duplicate, extracted data. The primary outcome was the difference in the presence or absence of white spots between experimental and control patients for parallel design studies, and between experimental and control quadrants, for split-mouth design studies. Potential sources of heterogeneity were examined. Sensitivity analyses were undertaken for the items assessed for quality and publication bias. MAIN RESULTS: The primary outcome of the review was the presence or absence of white spots by patient at the end of treatment. Secondary outcomes included any quantitative assessment of enamel mineral loss or lesion depth. Other outcomes such as differences in size and severity of white spots, any patient based outcomes, such as perception of white spots could not be included because there were insufficient data. Fifteen trials, with 723 participants, provided data for this review. None of the studies fulfilled all of the methodological quality assessment criteria. There is some evidence that a daily sodium fluoride mouthrinse reduces the severity of enamel decay surrounding a fixed brace (weighted mean difference for lesion depth -70.0; 95% CI -118.2 to -21.8) and that use of a glass ionomer cement for bracket bonding reduces the prevalence (Peto OR 0.35; 95% CI 0.15 to 0.84) and severity of white spots (weighted mean difference for mineral loss -645 vol%.microm; 95% CI -915 to -375) compared with composite resins. REVIEWERS' CONCLUSIONS: There is some evidence that the use of topical fluoride or fluoride-containing bonding materials during orthodontic treatment reduces the occurrence and severity of white spot lesions, however there is little evidence as to which method or combination of methods to deliver the fluoride is the most effective. Based on current best practice in other areas of dentistry, for which there is evidence, we recommend that patients with fixed braces rinse daily with a 0.05% sodium fluoride mouthrinse. More high quality, clinical research is required into the different modes of delivering fluoride to the orthodontic patient.

Dental Caries↗
PubMed2006

Home-based chemically-induced whitening of teeth in adults.

BACKGROUND: During the last decade tooth whitening products have become widely available in the USA for sale over-the-counter or dispensed by dentists for use at home. With the current rapid growth in demand for tooth whitening it is imperative that the dental community base its recommendations to patients on sound scientific evaluations conducted in well-designed and independent studies. OBJECTIVES: To evaluate the effectiveness (versus a placebo or another active product) and side effects of over-the-counter or dentist-dispensed chemically-based tooth whitening products designed for home use. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2005, Issue 3); MEDLINE (January 1966 to September week 2 2005); and EMBASE (1988 to week 39 2005). The tables of content of selected dental journals published since 1995 were searched for additional references. Written requests for additional studies and information were mailed to experts in this area of research. After a final set of studies was identified, the list of references reported in the included reports was reviewed to identify additional studies. Studies published in English and non-English were considered in this review. SELECTION CRITERIA: Randomised controlled trials and quasi-randomised controlled trials of dentist-dispensed or over-the-counter tooth whitening products with a chemical action (rather than abrasive action), for home use. DATA COLLECTION AND ANALYSIS: Screening of titles and abstracts, data extraction and quality assessment were undertaken independently and in duplicate. MAIN RESULTS: A total of 416 articles were identified, 25 of which met the inclusion criteria and presented data that could be used in the analysis. All included trials measured effectiveness immediately after 2 weeks of product application. Only 13 studies reported outcome data 1 week after the 2-week application period, and of those only six reported outcome data after 1 month or longer. Four of the included trials were assessed as at moderate risk of bias and the remainder at high risk of bias. All trials were sponsored by the manufacturers of tooth whitening products. Six trials compared different whitening products (gel in trays, paint-on films and whitening strips) with placebo/no treatment and all analyses showed the products to be effective, although most comparisons were based on single trials. Nineteen trials compared different whitening products with each other. There was only one meta-analysis which included more than one trial which showed statistically significant differences between the different whitening products. Strips (5.5% to 6.5% hydrogen peroxide(HP)) are more effective than gel in tray at 10% carbamide peroxide (CP) mean difference 1.82 (95% confidence interval (CI) 0.26 to 3.38). All of these trials were assessed as of high risk of bias. 'Mild' to 'moderate' tooth sensitivity and gingival irritation were the most common side effects. The whitening strips and products with high concentrations of HP caused more users to complain from tooth sensitivity. The protocols for preparation of participants prior to bleaching were inconsistent among the studies. Data on baseline scores of whiteness were not reported by the majority of the studies. The current evidence base on tooth whitening products suffers from methodological and publication biases. AUTHORS' CONCLUSIONS: There is evidence that whitening products work when compared with placebo/no treatment. There are differences in efficacy between the products, mainly due to the levels of active ingredients, hydrogen peroxide and carbamide peroxide. All trials were however short term and the majority of the studies were judged to be at high risk of bias and were either sponsored or conducted by the manufacturers. There is a need for pragmatic long-term and independent clinical studies that include participants representing diverse populations. There is also a need to evaluate long-term harms. Several studies reported (where measured) the common side effects of tooth sensitivity and gingival irritation, and people should be informed of this.

Adult↗
PubMed2006

Detection of Epstein-Barr virus (EBV) in the oral mucosa of renal transplant patients.

The purpose of this study was to determine the prevalence of Epstein-Barr virus (EBV)-DNA in the oral mucosa of renal transplant patients and observe the efficacy of mouth rinses with phosphate-buffered saline (PBS) to eliminate EBV present in the saliva. Lingual, gingival, and buccal cytobrushings were obtained from normal oral mucosa of 10 renal transplant patients and 10 normal subjects, and were examined through polymerase chain reaction (PCR), before and after rinses with PBS. EBV-DNA was detected in 86.6% of renal transplant recipients and in 46.6% of healthy subjects. No significant difference was observed between oral scrapes obtained before and after rinses with PBS with regard to detection of EBV-DNA. Our results suggest that the use of PCR to detect the presence of EBV-DNA in oral mucosa in the absence of specific lesions gives rise to the problem of identifying the viral replication sites. In addition, PBS was not effective at minimizing contamination by saliva.

DNA, Viral↗
PubMed2004

Protective effect of alpha-tocopherol in head and neck cancer radiation-induced mucositis: a double-blind randomized trial.

BACKGROUND: the study was designed to test whether vitamin E (VE) provides oral mucosal protection in patients with irradiated cancers of the head and neck. METHODS: Fifty-four patients with cancer of the oral cavity and oropharynx were randomly assigned to rinse the oral cavity in an oil solution containing either VE or placebo before every conventional fraction of 2 Gy and again 8 to 12 hours later during the 5 to 7 weeks of radiotherapy (RT). RESULTS: Thirty-six events/167 patient-weeks (21.6%) and 54 events/161 patient-weeks (33.5%) of symptomatic mucositis were observed in VE and placebo groups, respectively (p =.038). VE reduced the risk by 36%. Subjective data at the end of the treatment revealed that VE decreased pain grades 2 to 3 during RT (3 of 28 patients vs 14 of 26 patients, p =.0001). No significant influence was detected in survival. CONCLUSION: VE decreased the incidence of symptomatic oral radio-induced mucositis in patients with cancer of the oropharynx and oral cavity.

Carcinoma, Squamous Cell↗
PubMed2003

Evaluation of hypermethylated tumor suppressor genes as tumor markers in mouth and throat rinsing fluid, nasopharyngeal swab and peripheral blood of nasopharygeal carcinoma patient.

The purpose of our study was to evaluate the frequency of hypermethylated tumor suppressor genes (TSGs) in peripheral blood, mouth and throat (M&T) rinsing fluid and nasopharyngeal (NP) swabs of nasopharyngeal carcinoma (NPC) patients. Six normal NP tissues, 43 M&T rinsing fluid, 37 NP swabs and 43 peripheral blood from healthy non-smokers and non-drinkers without a family history of NPC, and 30 NPC tumors and their matched body fluid were analyzed for the presence of hypermethylated p15, p16, Ras association domain family 1 (RASSF1A), E-cadherin, and death-associated protein kinase (DAPK) by methylation-specific PCR. Sequencing analysis was carried out on selected NPC tumors and body fluid samples. Twenty-nine (97%) tumors displayed methylation in at least 1 of the 5 genes. The methylation frequencies were 80% for p15, 77% for DAPK, 67% for RASSF1A, 53% for E-cadherin and 33% for p16. The frequency range of aberrant methylated genes in the body fluids were NP swabs (17-63%) and M&T rinsing fluid (17-50%). Methylation was found in <20% of peripheral blood for each respective gene. Methylation was, however, detected in 1 M&T rinsing fluid in which the primary tumor showed methylation free for RASSF1A. Five healthy individuals exhibited methylation for DAPK, or RASSF1A, or p15 in their body fluid samples. All body fluid samples of healthy controls showed methylation free for E-cadherin and p16. Epigenetic change is found frequently in NPC and the high detection rate in body fluids suggest its potential application in non-invasive screening of NPC or detection of residual carcinoma after treatment.

Adult↗
PubMed1999

Dental knowledge and attitudes among Arab schoolteachers in northern Israel.

A representative random sample of 597 Arab school-teachers in northern Israel, was surveyed regarding sources and levels of knowledge and attitudes about dental caries prevention. Data were measured according to a self-administered questionnaire from a 91.4 per cent response rate. When ranking the effectiveness of different caries preventive measures teachers on average listed optimal water fluoridation as a lower priority compared to toothbrushing, dental visits, fluoride mouthrinses and eating fewer sweet products. Placing of fissure sealants was ranked as the second least effective caries preventive measure, with 39.6 per cent not knowing the effectiveness. Only 68.5 per cent of the school-teachers were aware of the anti-bacterial role of fluoride, and only a small minority knew of fluoride's potential in healing incipient caries. Teachers seemed less motivated to being involved in dental health school programmes which involved dedicating school time and their active involvement, such as fissure sealant programmes at school, supervision of brushing and flossing, and school mouthrinsing programmes. They revealed positive attitudes towards: informing parents about the importance of oral hygiene and teaching children about preventive dentistry. Teachers' main reported source of knowledge was the dental office. It is the responsibility of the dental profession to ensure that updated knowledge is correctly conveyed to schoolteachers, who are an important and potentially influential sector of dental health consumers and health education agents.

Adult↗
PubMed2002

Caries reductions related to the use of fluorides: a retrospective cohort study.

AIM: To test whether topical fluoride regimes provided additional caries protection to the first molar teeth of children exposed to fluoridated toothpaste and optimally fluoridated water supplies. PARTICIPANTS AND METHODS: This two-year retrospective cohort study included 660, 8-year-old-children. A cluster sampling technique was used to select three groups of 220 children. Group 1 was selected from schools using fluoride mouthrinses (Programme 1). Group 2 was selected from schools applying fluoride gel (APF 1.23%) in addition to the weekly fluoride mouthrinse (Programme 2). Oral health education and oral hygiene instruction were provided to both groups. The control group was selected from schools in the same area that had not adopted any oral health preventive programme. All children were exposed to optimally fluoridated water and fluoridated toothpaste for the last two years or more. Participants were examined for DMFS scores of their first molars using WHO criteria by one examiner (MLRS). RESULTS: The percentage caries free children in Control, Programme 1 and Programme 2 were 55%, 65% and 65.5%, respectively. The differences between Programme 1 and 2 in relation to the Control Group were statistically significant (P < 0.05). There was no difference between Programme 1 and 2 (P = 0.92). CONCLUSIONS: Weekly fluoride rinsing combined whether or not with fluoride gel applications once every three months, provided additional caries-preventive benefits to children with high levels of caries and exposed to optimally fluoridated drinking water and toothpaste. There was no difference in caries levels between children having fluoride rinses and those having fluoride rinses and fluoride gel.

Acidulated Phosphate Fluoride↗
PubMed2002

Cysteine challenge testing: a powerful tool for examining oral malodour processes and treatments in vivo.

Gram-negative oral bacteria rapidly produce the odorant hydrogen sulphide from cysteine. It provides a major part of the oral malodour bouquet while causing a corresponding decrease in the oxidation-reduction potential (Eh). A low Eh favours oral putrefaction and malodour occurrence. Challenge testing with cysteine (5ml of 6mM for 30 seconds) enabled evaluation of: the contribution of tongue and teeth bacteria to overall oral malodour; the effectiveness of tongue and tooth brushing, tooth scraping, gum chewing and mouthrinsing with different agents in reducing oral malodour. Successive cysteine challenge tests for 20 minute periods at selected times in a seven hour experiment were effective for assessing the magnitude and duration of an agent's effectiveness. Brushing the teeth reduced malodour modestly. So did tongue scraping and gum chewing. In contrast, brushing the tongue dorsum, especially the posterior half was remarkably effective, which confirmed it as a major site of oral malodour contribution. Rinses containing various actives showed wide variation in effectiveness. The experiments demonstrated that cysteine challenge testing is potentially a aluable tool for assessing the ability of the oral bacteria to produce malodour and for assessing agents designed to inhibit such production.

Anti-Infective Agents, Local↗
PubMed2004

The use of essential oils to treat snoring.

Snoring is a very common social inconvenience. This double-blind study suggests a significant reduction in snoring reported by bed partners in a group of snoring volunteers using either an essential oil spray or gargle formulation. Possible modes of action of the essential oils are discussed.

Administration, Inhalation↗
PubMed2005

A clinical study: Melaleuca, Manuka, Calendula and green tea mouth rinse.

A novel mouthrinse (IND 61,164) containing essential oils and extracts from four plant species (Melaleuca alternifolia, Leptospermum scoparium, Calendula officinalis and Camellia sinensis) were tested. This study aimed to evaluate the safety, palatability and preliminary efficacy of the rinse. Fifteen subjects completed the Phase I safety study. Seventeen subjects completed the Phase II randomized placebo-controlled study. Plaque was collected, gingival and plaque indices were recorded (baseline, 6 weeks, and 12 weeks). The relative abundance of two periodontal pathogens (Actinobacillus actinomycetemcomitans, Tanerella forsythensis) was determined utilizing digoxigenin-labeled DNA probes. ANCOVA was used at the p = 0.05 level of significance. Two subjects reported a minor adverse event. One subject withdrew from the study. Several subjects objected to the taste of the test rinse but continued treatment. Differences between gingival index, plaque index or relative abundance of either bacterial species did not reach statistical significance when comparing nine placebo subjects with eight test rinse subjects. Subjects exposed to the test rinse experienced no abnormal oral lesions, altered vital signs, changes in liver, kidney, or bone marrow function. Larger scale studies would be necessary to determine the efficacy and oral health benefits of the test rinse.

Adult↗
PubMed2001

Detection of cationic surfactants in oral rinses and a disinfectant formulation using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

Three commercial oral rinses and one commercial disinfectant formulation were analyzed for the presence of cationic surfactants using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) in the positive ion mode. The product labels on these formulations indicate the presence of cetylpyridinium chloride, tetraalkylammonium or trialkylbenzylammonium chlorides. The resulting MALDI-TOF mass spectra only showed cetylpyridinium, tetraalkylammonium, and trialkylbenzylammonium ions, apparently due to the dissociation of the salts in the ion source. We confirmed the presence of cetylpyridinium salt in the three oral formulations, whereas the disinfectant formulation consisted of a complex mixture of the salts of dioctyldimethylammonium, didecyldimethylammonium, benzylmyristyldimethylammonium, decyloctyldimethylammonium, benzyldecyldimethylammonium, and benzylcetyldimethylammonium. This work demonstrates again the potential for using meso-tetrakis(pentafluorophenyl)porphyrin as a matrix in the MALDI-TOFMS analysis of low molecular weight compounds. This study also demonstrates that the mode of ionization of quaternary ammonium compounds (cationic surfactant salts) under MALDI conditions is by dissociation, leading to the detection of only the positively charged moieties.

Cations↗
PubMed1999

Viadent usage and oral leukoplakia: a spurious association.

Oral rinse and toothpaste products (Viadent) containing Sanguinaria extract have been shown through extensive clinical trials to be effective against plaque build-up and gingivitis. To establish safety, a comprehensive research program was conducted, including a series of clinical studies and a number of animal studies to evaluate acute, subchronic, and chronic toxicity, and the potential for irritation of mucosal tissues. In 1990 and 1993, an Expert Panel reported on reviews of these data and concluded that Viadent products are safe for their intended use. Despite the large database of information to support the safety of Viadent products, Damm et al. (1999) recently raised the possibility that their usage may be causally associated with development of oral leukoplakia. However, a critique of this recent report shows that it does not fulfil criteria for establishing causation. In particular, the study does not show that exposure to Viadent preceded the onset of leukoplakia, it does not demonstrate dose-response or biological plausibility, and it suffers from selection and information bias and from potential confounding. Furthermore, upon critical evaluation, the Damm et al. (1999) report on a case-series is inconsistent with the weight of available clinical evidence showing that Sanguinaria extract-containing oral health care products cause no cytotoxic or significant irritant effects in the oral mucosa in human studies of up to 6 months duration. The animal data similarly do not support a causal association between Viadent usage and oral leukoplakia in humans. These data demonstrate that Sanguinaria extract and whole Viadent formulations are without significant irritation potential and have no effects on the oral mucosa, even in studies with life-long dietary exposure to Sanguinaria extract. The mutagenicity and genotoxicity data do not indicate that Sanguinaria extract or its components are genotoxic in vivo. The results of 2 GLP-compliant rat oncogenicity studies provide no evidence of any carcinogenic effect of Sanguinaria extract. In conclusion, the available clinical and animal data provide no support for and in fact argue strongly against the hypothesis that the use of Viadent toothpaste and/or oral rinse products may be causally associated with the development of leukoplakia in humans.

Alkaloids↗
PubMed1992

Growth characteristics of Sanguinaria canadensis L. cell suspensions and immobilized cultures for production of benzophenanthridine alkaloids.

Sanguinaria canadensis L. plants were harvested from a local forest and calli were initiated from leaf explants. The production of benzophenanthridine alkaloids (i.e. sanguinarine, sanguilutine, sanguirubine, chelerythrine, chelilutine and chelirubine) by S. canadensis cell grown in modified B5 and IM2 media was compared to the alkaloid content of rhizomes. Sanguinarine accounted for approximately 80% of the total alkaloid content of cultured cells (1.3%, g g-1) while sanguinarine and sanguirubine accounted for 70% of rhizome alkaloids (9.0%, g g-1). Sanguinarine, chelirubine and chelerythrine were the only known alkaloids detected in cultured S. canadensis cells. Maximum alkaloid production of cultures performed using B5 medium, containing half the original nitrate concentration, was observed following extracellular nitrate and sugar depletion. The scale-up of this culture was successfully performed in a 2-1 immobilization bioreactor. The consumption of sugar and nitrate as well as the oxygen (OTR) and carbon dioxide (CTR) transfer rates of the immobilized cell culture were monitored for 15 days. The maximum sugar and nitrate consumption rates were 1.8 g l-1 per day and 2.3 mM per day respectively. The maximum OTR and CTR of the immobilized cell culture were 0.8 mmol O2 l-1 h-1 and 0.95 mmol CO2 l-1 h-1 respectively. The sanguinarine yield of this culture reached 1.0% based on biomass dry weight (g g-1 dw) by day 15.

Alkaloids↗