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A clinical trial to assess the efficacy of sanguinarine-zinc mouthrinse (Veadent) compared with chlorhexidine mouthrinse (Corsodyl).

A single-blind crossover study was used to compare the ability of a 0.2% chlorhexidine mouthrinse (Corsodyl) with a sanguinarine-zinc mouthrinse (Veadent) to inhibit plaque and gingivitis. 14 volunteers starting with plaque-free mouths and optimal gingival health, rinsed with the preparations over two 19-day periods whilst refraining from all other oral hygiene procedures. At days 8, 15 and 19 of the trial, Corsodyl was significantly more effective at inhibiting both plaque and gingivitis. The findings of this study would suggest that the Veadent mouthrinse would at most only have a limited rôle as an inhibitor of plaque and gingivitis.

Adult↗

The use of repeated measures analysis of variance for plaque and gingival indices.

Clinical trials for anti-gingivitis and anti-plaque agents commonly use the mean of Silness and Löe plaque indices and Löe and Silness gingival indices as response variables. The aim of this report is to determine if data from anti-plaque and anti-gingivitis clinical trials using Silness and Löe plaque indices and Löe and Silness gingival indices satisfy conditions necessary for the use of the univariate or multivariate approach to repeated measures. These conditions are multivariate normality, homogeneity of variance-covariance matrices, and for the univariate approach, a type-H variance-covariance matrix. Data from 5 separate clinical trials representing a wide range in sample size, pretreatment mean gingival and plaque indices and treatment effects were used to test these conditions. Either the univariate or multivariate approach to repeated measures was found to be appropriate for both responses of the 5 clinical trials. Thus, means of Silness & Löe and Löe and Silness gingival indices meet the necessary conditions for use of either the univariate and/or multivariate approach to repeated measures. However, significant time-treatment interactions are a common occurrence in these types of clinical trials and must be evaluated carefully. The analyses in this study were carried out using SAS. Other mainframe statistical software packages and many micro-computer statistical software packages have routines to analyze repeated measures experiments with analysis of variance methods. However, some of the packages may omit the multivariate approach to repeated measures or may not include interactions between within-subject and between-subject effects. These packages should be used with caution.

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Comparative antiplaque activity of sanguinarine and chlorhexidine in man.

This clinical investigation examined the effect of a sanguinarine extract on bacterial plaque growth in man. Three different mouthrinses were examined: (i) Veadent containing 0.03% sanguinarine and 0.2% zinc chloride (test rinse); (ii) a vehicle solution containing all the excipients of Veadent except the 0.03% sanguinarine (control rinse); (iii) Hibident a 0.2% chlorhexidine digluconate formulation (positive control rinse). The trial in which 12 dental students participated, was designed as a single-blind, cross-over study. During 3 experimental periods of 18 days, the participants refrained from mechanical oral hygiene and rinsed twice a day with one of the above mentioned solutions. Between experimental phases, a wash-out period of 11 days was instituted. In each subject, 4 teeth were randomly selected for assessment. Clinical evaluations were performed at days 1 (0, 4, 8, 12 hours), 2, 4, 11 and 18. The plaque on the buccal surfaces of the selected teeth was disclosed with neutral red 0.05% and colour slides taken. The % of the tooth surface covered with plaque was calculated planimetrically from these colour slides. The present results show an excellent anti-plaque effect with Hibident, a very small effect with Veadent and a negligible effect with the vehicle solution without the sanguinarine. These findings would suggest that the Veadent mouthrinse would have at most only a limited role as a plaque inhibitor.

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A comparison of natural product, triclosan and chlorhexidine mouthrinses on 4-day plaque regrowth.

There is a continuing search for ingredients to enhance the chemical plaque inhibitory action of oral hygiene products. Sanguinarine, other natural extracts and triclosan have already been used in products. The aim of this study was to evaluate a number of triclosan and natural product rinses for effects on plaque regrowth. In particular, the influence of other rinse components were assessed, notably sodium lauryl sulphate (SLS) and zinc. The study was a randomised, blind, 9-cell cross-over design to measure the effects of each rinse on 4-day plaque regrowth from a zero baseline. 15 volunteers rinsed 2x daily with each product and plaque was recorded by area and score. The 0.2% chlorhexidine rinse (positive control) was significantly more effective, and the saline rinse (negative control) significantly less effective, than other rinses. Sanguinarine alone was little different from saline and the addition of zinc made a modest improvement in activity. The 3 triclosan/SLS rinses were more effective than the sanguinarine rinses but similar to their minus triclosan control rinse. A natural product/SLS experimental rinse was second to chlorhexidine and, in many analyses, significantly better than all other rinses, but caused some oral erosions. The results indicate that the plaque inhibitory properties of basic ingredients such as SLS may be difficult to enhance or surpass. However, the possible range of recipes, particularly using natural ingredients, provides scope for research and development in the field of oral hygiene products.

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A model for studying the effects of mouthrinses on de novo plaque formation.

The aim of the present study was to describe a 4-day no oral hygiene model to assess the pattern of de novo plaque formation and to use this model to appraise the potential of some mouthwash preparations to retard or inhibit plaque formation in the human dentition. 10 subjects were recruited for the trial. During a preparatory period, the participants were exposed to repeated professional plaque control and given oral hygiene instruction to eliminate signs of gingivitis. At the end of the preparatory period, each participant received a final professional tooth cleaning and was subsequently told to abstain from mechanical plaque control efforts for the next 4 days. They were asked to rinse twice daily for 60 s with 10 ml varying test solutions. On Day 4, the volunteers were exposed to a new clinical examination and the presence and amount of plaque were examined by the use of the plaque index system (P1I). The participants were subsequently given a professional tooth cleaning and asked to exercise proper self performed plaque control during the next 10 days. A new test period was then initiated. 6 different mouthwash preparations were tested in each subject namely, (1) placebo (a negative control rinse), (2) Veadent mouthrinse, (3) Listerine mouthrinse, (4) 0.06% triclosan + polyvinyl phosphonic acid (PVPA), (5) 0.06% triclosan + phenolic flavor and (6) 0.12% chlorhexidine digluconate (a positive control rinse). The results from the study revealed that the mean P1I values for individuals, groups of teeth and tooth surfaces provide an adequate but gross overall estimation of the potential of a given mouthrinse to retard/inhibit plaque build up. More detailed information on the effects of the test rinses could be obtained by data describing the % distribution of different P1I score categories; a high frequency of score 0 describes the potential of a mouthrinse to maintain tooth surfaces free from plaque while a low frequency of score 2/3 describes the ability of a treatment to retard/prevent gross plaque formation. The plaque pattern displays finally allowed assessment of the magnitude of plaque prevention, in comparison to the positive and negative controls, that could be achieved by a given compound in various parts and surfaces of the dentition. In this model, all test rinses (i) were significantly more effective than the placebo rinse in retarding de novo plaque build up and (ii) had a minor effects on plaque build up in the maxillary molars and at the approximal surfaces.(ABSTRACT TRUNCATED AT 400 WORDS)

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Antioxidative activities of some chemotherapeutics. A possible mechanism in reducing gingival inflammation.

Inflammatory periodontal diseases are related to dental plaque formation. Increase in the perfusion of the inflamed tissue results in increased oxygen supply. Although oxygen has healing effects, it is bound to be a mediator of peroxidation in biological membranes. Chemotherapeutic agents such as chlorhexidine, listerine, sanguinarine, and cetylpridinium chloride and oral antibiotics such as tetracycline HCl and doxycyline were tested for their antioxidative activities. While doxycycline has the highest antioxidant activity in lower volumes (0.1 ml), sanguinarine, listerine and a pace after them, tetracycline HCl, had similar effects in higher volumes (0.3 and 0.4 ml). The results showed that in addition to their antiseptic or antimicrobial effects, these preparations have an antioxidative activity against spontaneous oxidation.

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2 multi-center trials assessing the clinical efficacy of 5% sanguinarine in a biodegradable drug delivery system.

A biodegradable drug delivery system containing 5% sanguinarium (Sa) was compared to vehicle control (VC), scaling and root planing (SRP), and supragingival plaque control (SPC) in the treatment of adult periodontitis in 2 well-controlled clinical trials. Studies were 4-quadrant (split mouth) designs at 2 centers each, having 94 (Study A) and 107 (Study B) patients. All patients had at least 3 pockets between 5 and 9 mm that bled on probing, in each quadrant. Probing pocket depth (PD), clinical attachment level (AL), bleeding on probing (BOP), and plaque index were recorded at baseline, 14, 30, 60, and 90 days. All treatments gave statistically significant reductions from baseline for PD and BOP, and significant gains for AL. For PD reduction, SRP was superior to all test groups at all time points in both studies (p < 0.001). Sa was superior to VC in Study A at 14 and 30 days and to SPC at all time points. For AL gain at 90 days, in both studies, SRP gave gains of 0.42 and 0.78 mm respectively with superiority seen over the SPC group at 90 days (p < 0.001) in study A only, For BOP reduction, in Study A SRP was superior to Sa, VC, and SPC at 60 and 90 days (p < 0.005) and in Study B superiority to Sa and VC was at 90 days and to SPC at 60 days (p < 0.05). Sa was superior to VC for pocket depth in deep pockets only. Sa failed to demonstrate superiority over VC on a consistent basis. Analysis of residual Sa indicates that Sa potency was insufficient to show an advantage beyond clinical effects inherent in treatments with VC and SPC.

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Effectiveness of Veadent as a plaque-inhibiting mouthwash.

The aim of this study was to compare the effect of the commercially available Veadent mouthwash and chlorhexidine on plaque formation. Plaque accumulating during two 5-day periods was recorded in a group of 10 students. During the experimental periods, the test subjects abstained from mechanical cleaning of the teeth, and chewed sucrose-containing chewing gum every 4th h in order to enhance plaque formation. They also rinsed with either chlorhexidine or Veadent twice a day according to the manufacturer's recommendations. Chlorhexidine mouthrinses resulted in significantly lower plaque scores than did Veadent in the present short-term model study.

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Relationship between oral pain and ethanol concentration in mouthrinses.

Previous reports have indicated that certain mouthrinses, even when used as directed can induce oral pain. In order to help determine the causal agent(s), various commercially available mouthrinses, as well as control solutions, were tested in a psychophysical study in which subjects rated categories of pain during and after mouthrinsing. More specifically, the studies tested the effects of ethanol concentration on induced pain. The results show that there is a direct relationship between ethanol content and the amount of induced pain. Furthermore, the amount of pain was found to increase with time of rinsing, and to slowly decrease after cessation of rinsing. Lastly, comparison of ethanol/water controls with a marketed product (Clear Choice) matched for ethanol content showed that, while ethanol was the key factor in mouthwash-induced oral pain, other presently unidentified agents can also add to the effect.

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Effects of sanguinarium, chlorhexidine and tetracycline on neutrophil viability and functions in vitro.

The effectiveness of an ideal antimicrobial agent depends on its ability to kill microbes with minimal toxicity to host cells. Depending on the treatment regimen, antimicrobial agents come into contact with host cells for various intervals of time. Sanguinarium (SANG), chlorhexidine (CHX) and tetracycline (TET) are 3 antimicrobial agents frequently used in the management of periodontal infections. However, their effects on host immune cells during different treatment regimens are not known. Due to their ability to serve as the first line of host defense against microbial infections, we have compared the effects of these antimicrobial agents on human neutrophil functions and viability. The results show that SANG is not lytic to neutrophils from peripheral blood or crevicular fluid, at all concentrations tested. However, exposures of neutrophils to very low concentrations of SANG (0.001%) inhibits neutrophil chemotaxis, oxidative metabolism and degranulation within 5 min. Increasing the exposure time results in a similar inhibition of neutrophil functions, albeit at 50-100 fold lower concentrations of SANG. CHX rapidly disrupts the cell membrane of both crevicular and peripheral blood neutrophils at concentrations above 0.005% within 5 min, and inhibition of all neutrophil functions is due to its lytic properties. While TET is least toxic to neutrophils, a dose dependent inhibition of neutrophil functions is dependent on the calcium concentrations of the cellular environment, and is observed only above 0.04% or higher concentrations in the absence of calcium. The data suggest that a critical cumulative concentration of these drugs is essential for their toxicity and inhibition of neutrophil functions. Therefore, both the length of exposure and the dose of the drug both are critical while considering the effectiveness of SANG, CHX or TET in the treatment of infections. Furthermore, due to differences in their mechanisms of action, the consequences of their effects on neutrophils may have significant bearing on tissue pathology as well as on their therapeutic efficacy.

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Cytotoxicity of sanguinarine chloride to cultured human cells from oral tissue.

The in vitro cytotoxicity of sanguinarine chloride, a dental product used in the treatment of gingivitis and plaque, was compared using cell lines and primary cells from oral human tissues. For the established cell lines, sanguinarine chloride exhibited similar potencies to S-G gingival epithelial cells and to KB carcinoma cells, whereas HGF-1 gingival fibroblasts were more tolerant. However, a gingival primary cell culture was more sensitive to sanguinarine chloride than were the established cell lines. Detailed studies were performed with the S-G cells. The 24-hr midpoint (NR50) cytotoxicity value towards the S-G cells was 7.6 microM, based on the neutral red cytotoxicity assay; vacuolization and multinucleation were noted. When exposed to sanguinarine chloride for 3 days, a lag in growth kinetics was first observed at 1.7 microM. Damage to the integrity of the plasma membrane was evident, as leakage of lactic acid dehydrogenase occurred during a 3 hr exposure to sanguinarine chloride at 0.1275 mM and greater. The cytotoxicity of sanguinarine chloride to the S-G cells was lessened in the presence of an S9 hepatic microsomal fraction from Aroclor-induced rats or by including fetal bovine serum (15%) in the exposure medium. Progressively increasing the pH from 6.0 to 7.8 enhanced the potency of sanguinarine chloride, presumably due to the enhanced uptake of the lipophilic alkanolamine form, as compared to that of the cationic iminium form.

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Randomized controlled clinical trials on agents used for chemical plaque control.

Taking into account the limitations of the daily self-performed oral hygiene the use of chemical agents that can be incorporated in dentifrice or mouth rinse formulations has been advocated. The present review deals with randomized controlled clinical trials of >or=6 months in duration, on the use of those agents and their effects on plaque and gingival inflammation.

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Effect of pravastatin on impaired endothelium-dependent relaxation induced by lysophosphatidylcholine in rat aorta.

AIM: To investigate the effects of pravastatin, a potent 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, on impaired endothelium-dependent relaxation induced by lysophosphatidylcholine (LPC), the major component of oxidized low-density lipoprotein, in rat thoracic aorta. METHODS: Both the endothelium-dependent relaxation response to acetylcholine and the endothelium-independent relaxation response to sodium nitroprusside of aortic rings were measured by recording isometric tension after the rings were exposed to LPC in the absence or presence of pravastatin to estimate the injury effect of LPC and the protective effect of pravastatin on the aortic endothelium, respectively. RESULTS: Exposure of aortic rings to LPC (1-10 micromol/L) for 30 min induced a significant concentration-dependent inhibition of endothelium-dependent relaxation to acetylcholine, but did not affect endothelium-independent relaxation in response to sodium nitroprusside. Pre-incubation of aortic rings with pravastatin (0.3-3 mmol/L) for 15 min and then co-incubation of the rings with LPC (3 micromol/L) for another 30 min significantly attenuated the inhibition of endothelium-dependent relaxation induced by LPC. This protective effect of pravastatin (1 mmol/L) was abolished by NG-nitro-L-arginine methyl ester (30 micromol/L), an inhibitor of nitric oxide synthase, but not by indomethacin (10 micromol/L), an inhibitor of cyclooxygenase. Moreover, protein kinase C inhibitor chelerythrine (1 micromol/L) the superoxide anion scavenger superoxide dismutase (200 kU/L), and the nitric oxide precursor L-arginine (3 mmol/L) also improved the impaired endothelium-dependent relaxation induced by LPC, similar to the effects of pravastatin. CONCLUSION: Pravastatin can protect the endothelium against functional injury induced by LPC in rat aorta, a fact which is related to increasing nitric oxide bioavailability.

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Remifentanil mimics cardioprotective effect of ischemic preconditioning via protein kinase C activation in open chest of rats.

AIM: To examine whether the protective effect of remifentanil preconditioning (RPC) on postischemic hearts is mediated by protein kinase (PKC) activation in comparison with ischemic preconditioning (IPC). METHODS: Male Sprague-Dawley rats were anesthetized and their chests were opened. The experiment was performed with chelerythrine (CHE, 2 mg/kg), GF109203X (0.05 mg/kg) protein kinase C (PKC) inhibitors administered before RPC (remifentanil 6 microg x kg(-1) x min(-1) x 3 cycle) or IPC, respectively. Infarct size (IS), as a percentage of the area at risk (AAR), was determined by triphenyltetrazolium staining. RESULTS: In groups subjected to IPC and RPC the IS/AAR were significantly reduced (IS/AAR from 52.7%+/-5.5% to 12.9%+/-3.4%, P<0.01 vs CON and 16.2%+/-6.4%, P<0.01 vs CON), respectively. CHE and GF, both PKC inhibitors, administered 5 min before RPC or IPC completely abolished the cardioprotective effect of RPC (IS/AAR: CHE+RPC 51.2%+/-5.0%, GF+RPC 53.6%+/-6.1%, P>0.05 vs CON) or IPC (CHE+IPC 53.7%+/-4.3%, GF+IPC 54.1%+/-6.2%, P>0.05 vs CON). The difference was not significant in any of the hemodynamic parameters between control and treatment groups during ischemia and reperfusion. CONCLUSION: Remifentanil confers myocardial protection against ischemic injury through a mechanism that is similar to IPC and involves PKC activation.

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Protein kinase C in angiotensin II signalling in neonatal rat cardiac fibroblasts. Role in the mitogenic response.

The mitogenic effects of angiotensin II on cardiac fibroblasts are mediated by membrane receptors that are classified as AT1. These receptors are prototypical of the seven transmembrane group of receptors that couple, via G-proteins, to phospholipase C, thereby generating the endogenous activator of protein kinase C, diacylglycerol. Phorbol ester activators of protein kinase C exhibit growth-promoting effects in many cell types, suggesting that this enzyme may be responsible for the growth effects of angiotensin II on cardiac fibroblasts. Both kinase assays and Western analysis demonstrated that angiotensin II does induce translocation of protein kinase C to the detergent-soluble, membrane compartment of cardiac fibroblasts. Although translocation is commonly interpreted to mean activation of protein kinase C, in situ assays on permeabilized cells failed to detect increased enzymatic activity in response to angiotensin II. Nonetheless, this hormone did activate protein kinase C, leading to activation of mitogen-activated protein (MAP) kinases. However, a PKC-independent pathway for activation of MAP kinases exists as well. Downregulation and inhibitor studies indicated that protein kinase C is not critically involved in angiotensin II-induced thymidine incorporation into DNA. Furthermore, phorbol esters that activate protein kinase C do not elicit a mitogenic response in these cells. In conclusion, the mitogenic effects of angiotensin II on cardiac fibroblasts are not simply explained by activation of protein kinase C.

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