Fluoride release and anti-erosive effects of dentifrices containing PVM/MA copolymers

Objective

To evaluate fluoride release from dentine discs and study the effects of dentine tubule occlusion and erosion prevention of dentifrices containing fluoride and PVM/MA copolymers in a cycling erosive challenge model.

Methods

Human dentine discs, 15 in each group, were eroded by 1.0% citric acid and treated by ProNamel^® (PRN, 1450 ppm fluoride), Colgate^® Total Sensitive (CTS, 1100 ppm fluoride), a prototype dentifrice containing 5000 ppm fluoride and 2% PVM/MA copolymers (PVD) and distilled water (control). Fluoride release from each dentine disc was evaluated every 2 h in a 12-h period. For cycling erosive challenges, dentine discs were treated by dentifrice slurries twice daily, followed by immersion in saliva and erosive challenges by orange juice. Dentine discs were stored in saliva between treatment cycles and the cycling erosive challenges were repeated for 15 days. On days 5, 10, and 15, size of dentine tubule openings and level of dentine tubule occlusion were evaluated with a 3D scanning microscope.

Results

PVD released more fluorides than other dentifrices in a 12-h period (p < 0.05). CTS released more fluorides than PRN at 2, 4, 6, and 8 h following a single application (p < 0.05). The size of the dentine tubules was smaller and the number of occluded dentine tubules was greater in the CTS and PVD groups than those in the control and PRN groups on day 15 of the erosive challenges.

Conclusion

Bioadhesive PVM/MA copolymers facilitate fluoride retention and release from dentine discs, and promote dentine tubule occlusion and erosion prevention when combined with hydrated silica particles.     

Pre-existing virus-specific CD8 T-cells provide protection against pneumovirus-induced disease in mice

Pneumoviruses such as pneumonia virus of mice (PVM), bovine respiratory syncytial virus (bRSV) or human (h)RSV are closely related pneumoviruses that cause severe respiratory disease in their respective hosts. It is well-known that T-cell responses are essential in pneumovirus clearance, but pneumovirus-specific T-cell responses also are important mediators of severe immunopathology. In this study we determined whether memory- or pre-existing, transferred virus-specific CD8⁺ T-cells provide protection against PVM-induced disease. We show that during infection with a sublethal dose of PVM, both natural killer (NK) cells and CD8⁺ T-cells expand relatively late. Induction of CD8⁺ T-cell memory against a single CD8⁺ T-cell epitope, by dendritic cell (DC)-peptide immunization, leads to partial protection against PVM challenge and prevents Th2 differentiation of PVM-induced CD4 T-cells. In addition, adoptively transferred PVM-specific CD8⁺ T-cells, covering the entire PVM-specific CD8⁺ T-cell repertoire, provide partial protection from PVM-induced disease. From these data we infer that antigen-specific memory CD8⁺ T-cells offer significant protection to PVM-induced disease. Thus, CD8⁺ T-cells, despite being a major cause of PVM-associated pathology during primary infection, may offer promising targets of a protective pneumovirus vaccine.     

113Cd Nuclear Magnetic Resonance (NMR) Study of the Inhibitory Effect of Methylvinylether/Maleic Acid (PVM/MA) Copolymer on the Alkaline Phosphatase of Escherichia coli

The inhibitory effect of PVM/MA copolymer on the alkaline phosphatase (AP) of E. coli was investigated. Kinetic studies indicated that enzyme inhibition was characterized by a reduction in both the Vmax and the Km. Addition of 1 mM zinc or magnesium ions to the reaction prevented inhibition of the enzyme by the copolymer. The inhibitory effect of the copolymer on alkaline phosphatase was also investigated using 113Cd NMR after exchange of the active center metal ions with 113Cd. The resulting Cd(II)6AP exhibited characteristic 113Cd resonances reflecting the environment of the A, B, and C metal binding sites of the enzyme's active center. Addition of copolymer resulted in a 113Cd NMR spectrum which indicated removal of 113Cd from the C site and formation of two distinct forms of the enzyme. Possible explanations for the 113Cd NMR results are discussed.     

The effect of a polyhexamethylene biguanide mouthrinse compared with a triclosan rinse and a chlorhexidine rinse on bacterial counts and 4-day plaque re-growth

OBJECTIVES: For various clinical applications, polyhexamethylene biguanide hydrochloride (PHMB) has been used for many years as an antiseptic in medicine. Recently, a 0.04% and a 0.12% PHMB mouthwash were shown to inhibit plaque re-growth and to reduce oral bacterial counts. In this study, a 0.2% PHMB mouthrinse (A) was compared with a positive control 0.12% aqueous chlorhexidine solution (B), a commercially available 0.3% triclosan/2.0% polyvinyl methyl ether maleic acid copolymer mouthrinse (Colgate Total Plax) (C), and a negative control placebo rinse (10% ethanol, flavour) (D). MATERIALS AND METHODS: The controlled clinical study was a double blind, randomized, four replicate cross - over design. Plaque re-growth was assessed with the Turesky et al. (1970) modification of the Quigley & Hein (1962) plaque index. The antibacterial effect was assessed by taking bacterial counts on the tooth surface (smears from the buccal surface of 16/26) and mucosa (smears from the buccal mucosa in opposite of area 16/26) after the professional prophylaxis and after the first rinse with the preparations on day 1 and prior to the clinical examination on day 5. Sixteen volunteers participated and, on day 1 of each study period were rendered plaque-free, ceased toothcleaning, and rinsed twice daily with the allocated mouthrinse. On day 5, plaque was scored and smears were collected according to the protocol. A 10-day wash-out period was carried out between each rinse evaluation. Data were analysed using ancova with Bonferroni HSD adjustment for multiple comparisons (colony forming units per sample) with a significance level alpha=0.05. RESULTS: The 0.2% PHMB mouthrinse (A) was significantly better at inhibiting plaque than the placebo (D), but significant less effective than the 0.12% aqueous chlorhexidine solution (B). There is no significant difference between A and the 0.3% triclosan/2.0% copolymer mouthrinse (C). Bacterial count reductions (tooth surface and mucosa) with PHMB (A) were significantly greater compared with the placebo (D) and triclosan (C), but significantly lower compared with chlorhexidine (B) (tooth surface) and equally effective compared with chlorhexidine (B) (mucosa). CONCLUSION: Consistent with previous studies, a PHMB mouthrinse was shown to inhibit plaque re-growth and to reduce oral bacterial counts, indicating that PHMB could be an alternative to established mouthrinses in preventive applications.     

Intranasal immunisation with recombinant adenovirus vaccines protects against a lethal challenge with pneumonia virus of mice

Pneumonia virus of mice (PVM) infection of BALB/c mice induces bronchiolitis leading to a fatal pneumonia in a dose-dependent manner, closely paralleling the development of severe disease during human respiratory syncytial virus infection in man, and is thus a recognised model in which to study the pathogenesis of pneumoviruses. This model system was used to investigate delivery of the internal structural proteins of PVM as a potential vaccination strategy to protect against pneumovirus disease. Replication-deficient recombinant human adenovirus serotype 5 (rAd5) vectors were constructed that expressed the M or N gene of PVM pathogenic strain J3666. Intranasal delivery of these rAd5 vectors gave protection against a lethal challenge dose of PVM in three different mouse strains, and protection lasted for at least 20 weeks post-immunisation. Whilst the PVM-specific antibody response in such animals was weak and inconsistent, rAd5N primed a strong PVM-specific CD8⁺ T cell response and, to a lesser extent, a CD4⁺ T cell response. These findings suggest that T-cell responses may be more important than serum IgG in the observed protection induced by rAd5N.     

Respiratory syncytial virus, pneumonia virus of mice, and influenza A virus differently affect respiratory allergy in mice

BACKGROUND: Respiratory viral infections in early childhood may interact with the immune system and modify allergen sensitization and/or allergic manifestations. In mice, respiratory syncytial virus (RSV) infection during allergic provocation aggravates the allergic T helper (Th) 2 immune response, characterized by the production of IL-4, IL-5, and IL-13, and inflammatory infiltrates. However, it is unclear whether the RSV-enhanced respiratory allergic response is a result of non-specific virus-induced damage of the lung, or virus-specific immune responses. OBJECTIVE: In the present study we investigated whether RSV, pneumonia virus of mice (PVM) and influenza A virus similarly affect the allergic response. METHODS: BALB/c mice were sensitized and challenged with ovalbumin (OVA), and inoculated with virus during the challenge period. Pulmonary inflammation, lung cytokine mRNA responses, and IgE production in serum were assessed after the last OVA-challenge. RESULTS: Like RSV, PVM enhanced the OVA-induced pulmonary IL-4, IL-5, and IL-13 mRNA expression, which was associated with enhanced perivascular inflammation. In addition, PVM increased the influx of eosinophils in lung tissue. In contrast, influenza virus decreased the Th2 cytokine mRNA expression in the lungs. However, like PVM, influenza virus enhanced the pulmonary eosinophilic infiltration in OVA-allergic mice. CONCLUSION: The Paramyxoviruses RSV and PVM both are able to enhance the allergic Th2 cytokine response and perivascular inflammation in BALB/c mice, while the Orthomyxovirus influenza A is not.     

The Pneumonia Virus of Mice (PVM) Model of Acute Respiratory Infection

Pneumonia Virus of Mice (PVM) is related to the human and bovine respiratory syncytial virus (RSV) pathogens, and has been used to study respiratory virus replication and the ensuing inflammatory response as a component of a natural host—pathogen relationship. As such, PVM infection in mice reproduces many of the clinical and pathologic features of the more severe forms of RSV infection in human infants. Here we review some of the most recent findings on the basic biology of PVM infection and its use as a model of disease, most notably for explorations of virus infection and allergic airways disease, for vaccine evaluation, and for the development of immunomodulatory strategies for acute respiratory virus infection.     

Comparison of myocardial velocities obtained with magnetic resonance phase velocity mapping and tissue Doppler imaging in normal subjects and patients with left ventricular dyssynchrony

PURPOSE: To compare longitudinal myocardial velocity and time to peak longitudinal velocity obtained with magnetic resonance phase velocity mapping (MR-PVM) and tissue Doppler imaging (TDI), and to assess the reproducibility of each method. MATERIALS AND METHODS: Longitudinal myocardial velocity was measured by TDI and MR-PVM in 10 normal volunteers and 10 patients with dyssynchrony. The reproducibility of MR-PVM and TDI was assessed on repeated measurements in the 10 normal volunteers. RESULTS: MR and TDI measurements of longitudinal myocardial velocity correlated well (r = 0.86) in both normal subjects and patients with dyssynchrony. However, myocardial velocities measured with MR consistently exceeded velocities measured with TDI. MR and TDI agreed strongly in measuring the time to peak velocity (r = 0.97). The reproducibility of TDI and MR-PVM appeared similar in measuring peak velocities (13.1% vs. 11.0%, respectively; P = NS) and time to peak velocity (9.1% vs. 5.7%, respectively; P = NS). CONCLUSION: Excellent correlation and reproducibility were observed between MR-PVM and TDI in measuring longitudinal myocardial velocity and time to peak velocity in both normal subjects and patients with dyssynchrony.