A randomised clinical trial to determine the abrasive effect of the tongue on human enamel loss with and without a prior erosive challenge.

OBJECTIVES: To investigate the abrasive effect of the tongue on human enamel loss with and without a prior dietary acid challenge in an in situ model. METHODS: A single centre, single blind, randomly allocated, split mouth, four treatment regimen, in situ study in healthy adult volunteers was undertaken. Twenty four subjects wore two lower intra-oral appliances each fitted with 4 human enamel samples 6h/day for 15 days. The samples were treated with either 50ml orange juice or water for 5min ex vivo 4x/day; prior to being licked or not licked with the subject's tongue for 60s. There were 2 samples per group per subject. Surface loss was measured by contact profilometry. RESULTS: 23 subjects completed the study with no adverse events. The mean loss of enamel at 15days was: 0.08µm for water without licking, 0.10µm with water and licking; 1.55µm with orange juice alone, 3.65µm with orange juice and licking. In the absence of erosive challenge, licking had no detectable effect on enamel loss p=0.28. Without licking, orange juice had a highly significant effect on loss compared to water, p<0.001. Erosive challenge followed by licking more than doubled the loss of enamel p<0.001. CONCLUSIONS: When enamel was exposed to orange juice prior to licking, tissue loss as a result of tongue abrasion of the eroded surface was increased, and double that of the erosive challenge alone. Licking enamel with the tongue had no perceptible effect on enamel loss in the absence of the erosive challenge. CLINICAL SIGNIFICANCE: Enamel wear resulting from tongue abrasion on tooth surfaces softened by acid challenge, can be an unavoidable consequence of oral function. This may account for the pattern of erosive toothwear on palatal and occlusal tooth surfaces, reinforcing the importance of restricting the frequency of dietary acid challenge in susceptible individuals.

In situ randomised trial to investigate the occluding properties of two desensitising toothpastes on dentine after subsequent acid challenge.

OBJECTIVES: The aim of the study was to determine in situ the relative abilities of two desensitising toothpastes to occlude dentinal tubules with or without acid challenge. MATERIALS AND METHODS: The study design was a single centre, randomised, split mouth crossover model examining four treatments over two periods. The primary outcome was the degree of occlusion proffered by two desensitising toothpastes [Sensodyne® Rapid Relief (8% strontium acetate, 1040 ppm sodium fluoride) and Colgate® Sensitive Pro-ReliefTM daily (8% arginine, 1450 ppm sodium monofluorophosphate)], a standard toothpaste (1450 ppm sodium fluoride) and water, after acid challenge. Healthy adult volunteers wore bi-lateral lower buccal appliances each with two dentine sections, receiving two treatments per study period. Samples were brushed twice a day with treatment, with two additional 3-min extra-oral acidic challenges applied ex vivo on days 3 and 4. A secondary outcome was the degree of occlusion attained in the absence of acid challenge. Examiners blinded to the study assessed occlusion by visual score of post-treatment scanning electron microscope images. RESULTS: All 28 participants completed the study. In the absence of acid challenge, occlusion scores for both desensitising toothpastes were similar and significantly better than control scores (p < 0.02). After acid challenge both desensitising toothpastes occluded more effectively than controls; however, occlusion scores for the strontium acetate paste were significantly greater than those of the arginine paste (p < 0.02). CONCLUSIONS: The occluding properties of the strontium acetate toothpaste were significantly more robust after acid challenge than those of the arginine toothpaste. CLINICAL RELEVANCE: Patients with hypersensitivity, regularly imbibing dietary acidic drinks, should be advised that Sensodyne® Rapid Relief provides robust tubule occlusion despite repeated acidic challenges.

Phosphorus removal from municipal wastewater by hydrous ferric oxide reactive filtration and coupled chemically enhanced secondary treatment: part I--performance.

This work examines the performance of a hydrous ferric oxide (HFO) reactive filtration (RF) process with coupled chemically enhanced secondary treatment (RECYCLE) for phosphorus removal from municipal wastewater (HFO-RF-RECYCLE). A 3-month, 0.95-ML/d (0.25-mgd) demonstration of HFO-RF-RECYCLE was performed at a municipal wastewater treatment plant equipped with oxidation ditches and secondary clarifiers. Influent to the plant averaged 6.0 mg/L phosphorus, with a tertiary effluent average of 0.011 mg/L phosphorus. Iron doses to the plant were low, at 5 mg/L. Inline recycling of HFO solution rejects to the plant influent resulted in a maximum 90.3%, dose-dependent reduction of phosphorus in the secondary effluent at 4.5 ML/d (1.2 mgd). Other results included reduction of total suspended solids and turbidity. A mass balance analysis was performed. We conclude that HFO-RF-RECYCLE may allow very low levels of phosphorus discharge from municipal wastewater treatment plants with a ferric-iron-based tertiary filtration process and residual recycling.

Phosphorus removal from municipal wastewater by hydrous ferric oxide reactive filtration and coupled chemically enhanced secondary treatment: part II--mechanism.

The removal mechanism of a hydrous ferric oxide (HFO) reactive filtration (RF) process with coupled chemically enhanced secondary treatment (RECYCLE) for phosphorus removal from municipal wastewater (HFO-RF-RECYCLE) was examined. A 0.95-ML/d (0.25-mgd) demonstration of HFO-RF-RECYCLE was performed at a municipal wastewater treatment plant equipped with oxidation ditches and secondary clarifiers. Influent to the plant averaged 6.0 mg/L phosphorus, with a 3-month tertiary effluent average of 0.011 mg/L phosphorus. In addition to aqueous geochemical modeling, experiments with surface charge, scanning electron microscopy, adsorptive capacity, thermal desorption, and most probable number of iron(III)-reducing bacteria were performed on samples from the system, to determine the major phosphorus-removal pathways. Results suggest that, in addition to filtration of particulate phosphorus, the low tertiary effluent total phosphorus result was achieved by adsorption.

Preventing fractures among older people living in institutional care: a pragmatic randomised double blind placebo controlled trial of vitamin D supplementation.

INTRODUCTION: Osteoporotic fractures in older people are a major and increasing public health problem. We examined the effect of vitamin D supplementation on fracture rate in people living in sheltered accommodation. METHODS: In a pragmatic double blind randomised controlled trial of 3 years duration, we examined 3,440 people (2,624 women and 816 men) living in residential or care home. We used four-monthly oral supplementation using 100,000 IU vitamin D(2) (ergocalciferol). As a main outcome measure, we used the incidence of first fracture using an intention to treat analysis. This was a multicentre study in 314 care homes or sheltered accommodation complexes in South Wales, UK. RESULTS: The vitamin D and placebo groups had similar baseline characteristics. In intention-to-treat analysis, 205 first fractures occurred in the intervention group during a total of 2,846 person years of follow-up (7 fractures per 100 people per year of follow-up), with 218 first fractures in the control group over 2,860 person years of follow-up. The hazard ratio of 0.95 (95% confidence interval 0.79-1.15) for intervention compared to control was not statistically significant. CONCLUSION: Supplementation with four-monthly 100,000 IU of oral vitamin D(2) is not sufficient to affect fracture incidence among older people living in institutional care.

A clinical study in situ to assess the effect of a food approved polymer on the erosion potential of drinks.

OBJECTIVES: The consumption of acidic soft drinks continues to rise as do concerns regarding effects of frequent intake. The aim of the study was to determine the effect of acidic soft drinks containing food approved polymers, on dental enamel. METHODS: The study design was a single blind, randomised, five-treatment crossover clinical trial involving 15 healthy dentate subjects. Subjects wore an upper removable acrylic appliance retaining two enamel specimens and consumed 250ml of beverage four times/day for 10 days. The following beverages were tested: (1) unmodified acidic soft drink, (2) experimental acidic soft drink with 0.02% polyphosphate, (3) experimental acidic soft drink with 0.02% polyphosphate and 0.01% calcium, (4) experimental acidic soft drink with 0.02% polyphosphate and 0.03% xanthan gum, and (5) mineral water. Tissue loss was measured at days 5 and 10 of each study leg using a profilometer. RESULTS: The order of erosion from most to least at day 10 was unmodified acidic soft drink>experimental acidic soft drink with polyphosphate>experimental acidic soft drink with polyphosphate+gum>experimental acidic soft drink with polyphosphate+calcium>mineral water. At day 10 the unmodified acidic soft drink was significantly (p=0.001) more erosive than all other drinks. CONCLUSIONS: Unmodified acidic soft drink with the addition of polyphosphate alone or combined with calcium or xanthan gum are all effective at reducing erosion of enamel compared with the unmodified soft acidic drink.

The protective effects of toothpaste against erosion by orange juice: studies in situ and in vitro.

OBJECTIVES: There has been a monumental increase in the consumption of soft drinks, fruit juices and sport drinks in the UK, the US, and many other countries. Previous investigations have demonstrated the erosive nature of these acidic soft drinks. The aim of this investigation was to determine the protective effects of an experimental fluoride-based toothpaste, containing sodium hexametaphosphate, against an erosive challenge on tooth enamel. METHODS: The erosion of enamel by orange juice compared the experimental toothpaste with a benchmark sodium fluoride paste and negative control, water, in a 15-day in situ model; and the same in an in vitro enamel erosion model. Flat, polished human enamel samples with a surface profile of +/-0.1mum, were exposed to the three regimens in the single blind, crossover clinical study mimicked in vitro. Depths of the resulting eroded areas were measured using a profilometer. RESULTS: There was significantly more erosive damage on the specimens exposed to the benchmark paste and water compared to the test paste in both the in situ and in vitro studies. CONCLUSIONS: The data provide further support for tooth brushing before meals. Results of this study further suggest the sodium hexametaphosphate containing paste could be used to provide significant erosion protection in susceptible individuals over that provided by conventional fluoride products.

Comparative study of enema retention and preference in ulcerative colitis.

BACKGROUND: Therapeutic enemas are often used to treat active colitis but their retention may be limited because of urgency to defecate. Some preparations may be better retained and tolerated than others because of their physical properties. AIM: To compare patient preference and retention of four therapeutic enemas, including a nicotine enema, in patients with ulcerative colitis (UC). METHODS: Twenty four patients with active UC received the four trial enemas-corticosteroid, 5-amino salicylate (5-ASA), and nicotine liquid enemas and a corticosteroid foam, in a randomised order, taking one enema on each of four successive nights. Patients scored them 1 to 4 for ease of administration and retention, degree of abdominal bloating, and for their overall preference. RESULTS: Fifteen patients rated nicotine their overall favourite or second favourite, compared with 14 for corticosteroid foam and 11 for 5-ASA and corticosteroid liquids, but this was not significant (p = 0.302). Overall, there was no significant difference in overnight retention. However, the nicotine enema tended to be less well retained in patients with milder urgency but a higher proportion retained it overnight with more severe urgency (p = 0.031 compared with 5-ASA enema). CONCLUSION: There was no significant difference in patient preference or overall duration of retention for the four enemas.

Plasma fibrinogen in ulcerative colitis: the effect of disease activity and nicotine therapy in a randomised controlled trial.

BACKGROUND: Smoking increases plasma fibrinogen and cardiovascular risk whereas transdermal nicotine may not. Fibrinogen is an acute phase protein and may reflect disease activity in ulcerative colitis. AIMS: To examine the effect of topical nicotine on plasma fibrinogen and any relationship between fibrinogen and ulcerative colitis disease activity. PATIENTS: Forty-eight non-smokers with moderately active ulcerative colitis. METHODS: Patients were randomised to 6 mg nicotine enema or placebo for 6 weeks, followed by open nicotine therapy for 4 weeks. Plasma fibrinogen was measured at baseline and after 6 and 10 weeks; at each assessment sigmoidoscopy with a rectal biopsy was performed. RESULTS.: At 6 weeks median plasma fibrinogen was 3.30 g/l on nicotine compared to 3.05 g/l on placebo, P = 0.90 when adjusted for baseline values. There was a correlation between fibrinogen and the UC disease activity index (UCDAI) at weeks 0 and 10, P = 0.036 and 0.033, respectively, and between fibrinogen and sigmoidoscopic grade at each assessment, P = 0.014, 0.021 and 0.034. Changes in fibrinogen did not correlate with changes in disease severity. CONCLUSIONS: There was no significant effect of nicotine enemas, in either direction, on plasma fibrinogen-this was raised in moderately active UC and correlated with the sigmoidoscopic grade of colitis and the UCDAI; however, fibrinogen was not sufficiently sensitive to be of practical clinical value.

Development of methods to enhance extrinsic tooth discoloration for comparison of toothpastes. 1. Studies in vitro.

BACKGROUND: The interaction of chlorhexidine with dietary chromogens to cause extrinsic dental staining has been exploited in vitro and in vivo to study tooth discoloration and its control. These studies in vitro investigated factors that might enhance stain formation, and evaluated formulations to inhibit the stain with the primary aim of devising a protocol for use in vivo. METHOD: The standard method cycled acrylic specimens through saliva, 0.2% chlorhexidine and tea on the hour 8 times per day and stain was measured using a spectrophotometer. Test interventions were 3 "whitening" toothpastes (A, P, R), a fluoride toothpaste (C) and water. In studies 1 and 3 interventions were at 09:00 and 16:00, and in studies 2 and 4 at 09:00 and 13:00. Between cycles, specimens remained dry in studies 1 and 2 and were maintained in water day and night in studies 3 and 4. Studies 5-7 determined the influence of tea temperature, exposure time and concentration, and chlorhexidine temperature and exposure time on stain development. Studies 8-10 modified the standard procedure using tea at triple strength and 50 degrees C, and assessed stain inhibition by toothpastes and water using optical density, colorimetric and visual assessment recordings. RESULTS: In studies 1-4, there were highly significant differences between interventions. Overall, the experimental whitening paste (P) produced the most stain inhibition, and water or the proprietary whitening paste (R), produced the least stain inhibition. More stain inhibition was seen with interventions at 09:00 and 16:00. Both tea concentration and temperature significantly influenced staining. Chlorhexidine temperature did not influence staining. Exposure time to tea and chlorhexidine had a small effect on staining. In studies 8 and 9, interventions at 09:00 and 16:00 were more effective; the most stain inhibition was with paste P and the least with water, paste R being intermediate. In study 10, P was the most effective and R the least effective interventions. CONCLUSIONS: These studies in vitro suggest that the chlorhexidine tea stain model can be manipulated to enhance stain and thereby should improve discrimination between stain inhibition formulations. The timing of interventions in the model appears to be important. These studies in vitro were used to plan a clinical protocol.

Development of methods to enhance extrinsic tooth discoloration for comparison of toothpastes. 2. Two-product clinical study.

BACKGROUND: Extrinsic staining of teeth is considered to be unsightly and a number of 'whitening' toothpastes have been formulated to inhibit or remove such tooth discoloration. The aim of this study was to compare the stain prevention of two toothpastes. METHOD: The study was a single-blind, randomised, placebo-controlled, crossover design, balanced for residual effects involving 24 healthy dentate volunteers. The treatments were as follows: (1) a whitening toothpaste product, (2) an experimental toothpaste formulation and (3) water. For each 4-day rinse period, subjects were rendered stain free on the teeth and tongue. Approximately on the hour from 09:00 to 16:00 hours, subjects rinsed with chlorhexidine mouth rinse for 1 min followed by warm black tea for 1 min. The treatment interventions were at 09:00 and 16:00 hours and before the chlorhexidine rinse. The toothpastes were rinsed as 3 g/10 ml water slurries and water as a 10 ml rinse each for 2 min. On day 5, subjects were scored for tooth and tongue stain intensity and area, and the product of these was calculated. The washout period was at least 9 days. RESULTS: Treatment differences for the teeth were highly significant but not for the tongue. Paired contrasts for tooth stain intensity, area and product were mostly all significantly in favour of reduced staining by the experimental formulation compared with water and the whitening product. There were no significant differences between water and the whitening product. CONCLUSIONS: Using a forced dietary staining method, the data support a tooth stain-inhibitory/-removal action for the experimental formulation, but not the whitening product.

A clinical study to assess the ability of a powered toothbrush to remove chlorhexidine/tea dental stain.

AIM: A single-center, single-blind, two-way crossover study was performed to compare the effects of an electric powered toothbrush with a conventional manual toothbrush at removing chlorhexidine/tea tooth staining. METHODS: This study used 24 subjects. During the week before the study, the subjects received a prophylaxis to remove all staining, plaque and calculus deposits. On the Monday of the following week, subjects returned to the clinic to receive a further prophylaxis. Under direct supervision, they then rinsed with a 0.2% chlorhexidine mouthrinse, immediately followed by a rinse with a warm black tea solution. This cycle was repeated hourly eight times throughout the day and on the following days until the Friday. Throughout this period, volunteers omitted all other forms of oral hygiene except rinsing with the chlorhexidine mouthwash. On the Friday, the level of stain was assessed both prior to and immediately after brushing with the allocated brush with toothpaste for 1 min. This was done in an adjoining room (out of sight of the clinical scorer). Subjects were then instructed to use the toothbrush at home according to their normal oral hygiene practices. On the following Friday, subjects returned to the clinic when the stain present was re-assessed. Each subject received a thorough prophylaxis to remove all plaque calculus and staining before starting the second period of the study and again on completion of the study. RESULTS: The study showed relatively little difference between the ability of the two brushes to remove stain at a single test brushing. However, there was some evidence that the powered brush was more effective than the manual brush in minimising stain level during the home use period, overall and in particular for gingival crescent sites. CONCLUSIONS: This study has suggested that the powered brush may become more effective at reducing dental stain, the longer the brush is used under normal home conditions.

Use of videotape to assess mobility in a controlled randomized crossover trial of physiotherapy in chronic multiple sclerosis.

OBJECTIVES: To determine to what degree assessment of mobility based on comparison of videotape recordings before and after courses of physiotherapy in patients with chronic multiple sclerosis (MS) is reliable, correlates with 'live' assessments and indicates benefit. DESIGN: Prospective data collection within a randomized crossover controlled trial of physiotherapy at home, as an outpatient, or 'no therapy' in 40 patients. SETTING: Hospital outpatients: outpatient and home physiotherapy. OUTCOMES: Mobility change based on a comparison of short video recordings before and after each treatment period was scored independently by two physiotherapists blinded to therapy type and other measures of outcome. Scores were compared with changes in the Rivermead Mobility Index (RMI) and other indices assessed by a physiotherapist in the patient's home. RESULTS: The two video observers agreed substantially on patient outcome. Changes in walking based on video correlated with RMI for home treatment (r = 0.41, p = 0.008) but not for hospital or no treatment periods (r = 0.14 and 0.15): video changes correlated with the 'live' assessor's global change score inconsistently ('no therapy' r = 0.48, p = 0.002, hospital r = 0.30, p = 0.06 and home r = 0.17, p = 0.30 treatment periods). Based on video data alone, improved mobility was evident following home therapy for only one observer but not for the other or the averaged scores of both. CONCLUSION: There was substantial agreement between two observers deciding on change in mobility based on independent blinded evaluation of short video sequences. However the correlations of these with 'live' assessments were variable. Physiotherapy had a less clear benefit on mobility based on video analysis alone compared with 'live' assessments. The study highlights the need for more objective measures of habitual mobility over longer periods.

Reduction in plasma total homocysteine through increasing folate intake in healthy individuals is not associated with changes in measures of antioxidant activity or oxidant damage.

BACKGROUND: Various mechanisms have been proposed to explain the association between plasma total homocysteine (tHcy) and risk of cardiovascular disease, including oxidative activity of homocysteine. OBJECTIVE: To explore the putative role of reactive oxygen species in the association between plasma tHcy and risk of cardiovascular disease in healthy individuals. DESIGN: A double-blind, placebo-controlled crossover intervention to increase folate intake through diet (increased consumption of folate-rich foods) and supplement (400 micro g folic acid) was carried out in 126 healthy men and women. Measurements were made of antioxidant activity in red blood cells and plasma, and products of oxidant damage in plasma. RESULTS: Diet and supplement-based interventions led to an increase in measures of folate status and a reduction in plasma tHcy. This was not associated with any significant change in measures of antioxidant activity (plasma and red blood cell glutathione peroxidase activity and red blood cell superoxide dismutase activity) or oxidant damage (plasma malondialdehyde), although an improvement in plasma total antioxidant capacity just failed to reach significance. CONCLUSIONS: In healthy individuals lowering plasma tHcy does not have any functional implications regarding oxidative damage.

A comparison of the effect of advice to eat either '5-a-day' fruit and vegetables or folic acid-fortified foods on plasma folate and homocysteine.

OBJECTIVE: To assess and compare the effects of natural folate (100 micro g) with those of folic acid from fortified sources (100 micro g/day) on plasma folate and homocysteine. DESIGN: Randomized controlled trial (parallel groups). SETTING: Men and women living in South Wales, UK. SUBJECTS: A total of 135 healthy individuals recruited from the local workforce and blood donor sessions. All subjects possessed the 'wild-type' CC genotype for C677T polymorphism in methylenetetrahydrofolate reductase (MTHFR). INTERVENTIONS: Subjects underwent one of the following dietary interventions for 4 months: (1) fortified diet-usual diet plus 100 microg/day folic acid from fortified foods; (2) natural folate diet-usual diet plus 100 microg/day folate from natural sources; (3) control-usual diet. RESULTS: The fortified group increased reported intake of folic acid from fortified foods compared to other groups (P<0.001) achieving an extra 98 microg/day (95% CI 88-108). The natural folate group increased reported intake of natural source folates compared with the other two groups (P<0.001), but achieved a mean increase of only 50 microg/day (95% CI 34-66). Plasma folate increased (P<0.01) by a similar amount in both intervention groups compared to controls (fortified group 2.97, 95% CI 0.8-5.1; natural group 2.76, 95% CI 0.6-4.9. Plasma homocysteine, vitamins B(6) and B(12) were not significantly changed. CONCLUSIONS: Subjects achieved increases in folate intake using fortified foods more easily than by folate-rich foods, however both sources increased plasma folate by a similar amount. These levels of intake were insufficient to reduce homocysteine concentrations in MTHFR CC homozygotes, but may be more effective in other genotypes.

Nerve morbidity following wisdom tooth removal under local and general anaesthesia.

Two hundred and one patients had unilateral removal of the lower third molars under local anaesthesia and a further 234 patients had either bilateral or unilateral removal under general anaesthesia. A total of 634 lower third molars were extracted by four experienced surgeons (two consultants and two senior grade staff). All patients were reviewed independently 1-week postoperatively and any sensory disturbance and its location was recorded. Patients with sensory disturbance were subsequently reviewed at 1 month and again at 6 months if recovery was not complete. This study demonstrated little difference in the adverse event rate per tooth extracted between procedures under local and general anaesthesia. However, within the general anaesthetic group, the few unilateral procedures showed evidence of higher risk, but the number was too small for valid satisfactory analysis. The risk of nerve morbidity was also greater where the duration of the procedure was longer than 15 minutes in unilateral cases.

Optimization of dietary folate or low-dose folic acid supplements lower homocysteine but do not enhance endothelial function in healthy adults, irrespective of the methylenetetrahydrofolate reductase (C677T) genotype.

OBJECTIVES: We sought to study the effect of low-dose folic acid supplementation or optimization of dietary folate intake on plasma homocysteine and endothelial function in healthy adults. BACKGROUND: Elevated homocysteine is associated with cardiovascular disease, but it is not known whether this relationship is causal. Individuals homozygous (TT) for the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene ( approximately 12% of the population) have increased homocysteine levels, particularly in association with suboptimal folate intake. METHODS: Healthy subjects (n = 126; 42 of each MTHFR genotype) were included in this cross-over study of three interventions of four months each: 1) placebo plus natural diet; 2) daily 400-microg folic acid supplement plus natural diet; and 3) increased dietary folate intake to 400 microg/day. RESULTS: At baseline, homocysteine was inversely related to plasma folate and was higher in TT homozygotes. For the whole group, plasma folate increased by 46% after dietary folate and by 79% after supplementation, with reductions of homocysteine of 14% and 16%, respectively. Within the genotype, TT homozygotes exhibited the most marked changes in these variables. Brachial artery endothelial function, as determined by a change in end-diastolic diameter in response to increased flow, was not changed by increased folate intake (98 +/- 73 microm at baseline, 110 +/- 69 microm after a high-folate diet, 114 +/- 59 microm after supplementation and 118 +/- 68 microm after placebo). Plasma von Willebrand factor antigen was unaltered. CONCLUSIONS: Optimization of dietary folate or low-dose folic acid supplementation reduces plasma homocysteine but does not enhance endothelial function, irrespective of the MTHFR (C667T) genotype.

Folate improves endothelial function in coronary artery disease: an effect mediated by reduction of intracellular superoxide?

Homocysteine is a risk factor for coronary artery disease (CAD). Folic acid lowers homocysteine and may improve endothelial function in CAD, although the mechanism is unclear. We investigated the effect of folic acid on endothelial function, homocysteine, and oxidative stress in patients with CAD. We also examined the acute effect of 5-methyltetrahydrofolate (5-MTHF), the principal circulating folate, on endothelial function in vivo and on intracellular superoxide in cultured endothelial cells. A randomized crossover study of folic acid (5 mg daily) for 6 weeks was undertaken in 52 patients with CAD. Ten further patients were given intra-arterial 5-MTHF. Endothelial function was assessed by flow-mediated dilatation (FMD). Folic acid increased plasma folate (P<0.001), lowered homocysteine by 19% (P<0.001), and improved FMD (P<0.001). FMD improvement did not correlate with homocysteine reduction. Malondialdehyde and total plasma antioxidant capacity, markers of oxidative stress, were unchanged. 5-MTHF acutely improved FMD (P<0.001) without altering homocysteine (P=0.47). In vitro, 5-MTHF abolished homocysteine-induced intracellular superoxide increase (P<0.001); this effect was also observed with folic acid and tetrahydrobiopterin. Our data support the beneficial effect of folic acid on endothelial function in CAD but suggest that the mechanism is independent of homocysteine. Reduction of intracellular endothelial superoxide may have contributed to the effect.

Studies on the effect of polyvinyl pyrrolidone on the activity of chlorhexidine mouthrinses: plaque and stain.

BACKGROUND, AIMS: Polyvinyl pyrrolidone (PVP) was shown in vitro to reduce chlorhexidine induced, dietary staining without affecting the uptake of the antiseptic to the test substrate. The aim of these studies in vivo was to determine whether PVP affected plaque and dietary staining by a low concentration chlorhexidine rinse. METHODS: The plaque and stain studies used a double blind, randomised 6, treatment crossover design involving healthy subjects with a high standard of oral hygiene and gingival health. The rinse formulations under test were: (A) aqueous alcohol (placebo control), (B) 0.03% chlorhexidine, (C) 0.06% chlorhexidine, (D) 0.06% chlorhexidine+1.2% PVP, (E) 0.06% chlorhexidine+5% PVP, (F) 0.06% chlorhexidine+10% PVP. In the plaque study, on day 1 of each period, subjects were rendered plaque free and then rinsed with 15 ml of the test rinse for 60 s. No further tooth cleaning was performed and subjects returned 24 h later for plaque scoring by area. In the stain study, on day 1 of each period, the tongue and teeth of each subject were rendered stain free. Subjects then rinsed under supervision for 60 s with 15 ml of the allocated rinse 8 x a day between 09:00 h and 17:00 h for 3 days. Immediately after each rinse with the test formulation, subjects rinsed for 120 s with 15 ml of warm black tea. Subjects were requested to also drink at least 5 cups of tea or coffee per day. On day 4, stain was scored by area and intensity from designated teeth and dorsum of the tongue. Washout periods were at least 7 days in both studies. RESULTS: Plaque areas were greatest with placebo and least with 0.06% chlorhexidine. Plaque scores increased with increasing concentrations of PVP in the 0.06% chlorhexidine rinse and were significantly higher than 0.06% chlorhexidine without PVP rinse. Tooth stain areas were comparable for placebo, 0.03% and 0.06% chlorhexidine rinses, but significantly reduced with the PVP/chlorhexidine rinses compared to the 0.06% chlorhexidine rinse. Tooth stain intensity was significantly increased with 0.06% chlorhexidine rinses compared to placebo and chlorhexidine/PVP rinses. Tongue stain area and intensity were significantly reduced with 5% and 10% PVP/chlorhexidine rinses compared to 0.06% chlorhexidine rinse. CONCLUSION: PVP, at the concentrations tested, reduced the stain propensity of a 0.06% chlorhexidine rinse but at the expense of some loss of plaque inhibition.