Displaying publications 1 - 20 of 32 in total

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  1. Chhabra N, Parolia A
    Materials (Basel), 2023 Jun 23;16(13).
    PMID: 37444849 DOI: 10.3390/ma16134535
    The objectives of this study were to compare the effects of various acid solutions combined with ultrasonics as an aid to remove mineral trioxide aggregate (MTA)-based root canal filling and to assess their effect on the surface topography and microhardness of root canal dentin.

    MATERIALS AND METHOD: Fifty human permanent single rooted and single canaled freshly extracted teeth were decoronated and sectioned apically to prepare the middle third of root sections of 5 mm length. The canals were prepared in a step-back manner. OrthoMTA was packed throughout the prepared canals. These root sections were incubated for one week and subsequently randomly allocated to five groups (n = 10) according to the OrthoMTA removal method: No treatment (NT); 5% glycolic acid + ultrasonics (5% GA+U); 10% glycolic acid + ultrasonics (10% GA+U); 10% citric acid + ultrasonics (10% CA+U); Distilled water + ultrasonics (DW+U). A 1 mm deep well was created within the coronal end of the set OrthoMTA. Wells were filled with each respective test solution and left for 5 min. Thereafter, further removal of OrthoMTA used a specific ultrasonic tip. Finally, the canals were flushed using 1 mL of the respective test solutions and activated with a Controlled Memory ultrasonic tip for two cycles of 20 s each followed by flushing with 1 mL of distilled water and paper point drying of the canals. Then, specimens were longitudinally split into two halves and examined under a scanning electron microscope (1000×) to assess the residual OrthoMTA and surface topography of root canal dentin. The Vickers surface microhardness of treated radicular dentin was measured using the HMV-2 microhardness tester.

    RESULT: Data were analysed using one-way ANOVA followed by Tukey's post hoc test. Significant differences for residual OrthoMTA were observed between (10% GA+U) with (5% GA+U), (10% CA+U), (DW+U) and (NT) (p value < 0.01). In the context of microhardness, (5% GA+U) and (10% GA+U) showed statistically significant difference compared to (NT), (10% CA+U) and (DW+U) (p value < 0.01).

    CONCLUSION: 10% GA+U was superior to other tested groups in removing OrthoMTA, but it substantially reduced dentin microhardness.

  2. Sharma S, Parolia A, Kanagasingam S
    Eur J Dent, 2020 Dec;14(S 01):S159-S164.
    PMID: 33167046 DOI: 10.1055/s-0040-1718240
    In the light of coronavirus disease 2019 (COVID-19), dentistry is facing unprecedented challenges. The closure of clinics has impacted dental health professionals (DHPs) not only financially but also psychologically. In this review, these consequences are discussed in detail to highlight the challenges that DHPs are facing thus far, in both developing and developed nations. Compromised mental health among DHPs is an important area that requires attention during this difficult period. Although, in previous pandemics, dentists have not worked on the frontline, the article discusses how their wide range of skillsets can be leveraged if another wave of COVID-19 pandemic appears. Finally, guidelines to reopen clinics and patient management have been discussed in detail that could serve as a quick reference guide for DHPs.
  3. Arunachalam S, Parolia A, Pau A
    Eur J Dent Educ, 2021 Dec 20.
    PMID: 34928527 DOI: 10.1111/eje.12744
    INTRODUCTION: Clinical audit is a quality improvement process that seeks to improve patient care and outcomes through the systematic review of care against explicit criteria and the implementation of change. The objective of this audit was to evaluate the quality of orthodontic chart documentation by dental undergraduates against established guidelines.

    MATERIALS AND METHODS: An audit checklist with 13 criteria for good documentation was adapted from guidelines proposed by the American Association of Orthodontists and British Orthodontic Society. Orthodontic chart documentation in 103 removable appliance therapy patients under 4th and 5th year dental undergraduates' care was retrieved from the electronic record of the University dental clinic and audited. The audit exercise explored in detail the thirteen criteria for good documentation and eight assessment attributes of the first criterion, namely, basic orthodontic examination. The level of compliance was measured as the percentage records meeting the criteria. The data were statistically analysed using SPSS 26.0 (SPSS, Inc., Chicago, IL, USA).

    RESULTS: There was no complete compliance for any of the criteria. Thirty-five (33.9%) patient charts reported basic orthodontic examination documentation adequately. Compliance was the highest for documentation of treatment modality (77.6%), appliance delivery encounters (77.6%), and appliance adjustment appointments (83.5%). About 51.4% of the 68 patient charts (treatment of 35 patients of the total 103 were in the progress stage) stated adequately the outcome of treatment. Only 22% of the 68 patient charts had the details for retention protocol. There was statistically significant difference in chart documentation between male and female students for basic orthodontic assessment and appliance delivery and patient instructions attributes.

    CONCLUSION: The clinical audit demonstrated poor compliance with the criteria for orthodontic chart documentation. The audit should be repeated after the provision of learning opportunities and self-critical analysis.

  4. Parolia A, Mohan M, Kundabala M, Shenoy R
    J Dent Educ, 2012 Mar;76(3):366-71.
    PMID: 22383607
    Teaching and learning activities in the dental clinic or hospital are a challenging area for students as well as teachers. With various teaching methodologies being used in dental schools around the world, gaining greater understanding of students' attitudes toward these methodologies would be useful for dental educators. The objective of this study was to explore the preferences of dental students in India about various aspects of lecture courses. A structured survey consisting of ten closed-ended questions was developed, and 2,680 undergraduate students from forty-three dental schools in India were approached via e-mail with a follow-up postal mailing. Of these, 1,980 students responded, for a response rate of 73.8 percent. Most of the students reported preferring lectures with the aid of PowerPoint and chalkboard. They preferred morning lectures from 8 am to 10 am for a maximum of thirty to forty minutes for each lecture, and they preferred to receive information about the lecture topic in advance. The students said that delivery of clinical demonstrations was beneficial after the lectures, and they preferred learning-based rather than exam-oriented education. The respondents also said that attendance should be made compulsory and that numerical marking of examinations should not be replaced by a grading system.
  5. Chen CL, Parolia A, Pau A, Celerino de Moraes Porto IC
    Aust Dent J, 2015 Mar;60(1):65-72.
    PMID: 25721280 DOI: 10.1111/adj.12275
    Dentine hypersensitivity (DH) occurs on exposed dentine and is dependent on the patency of dentinal tubules. This study compared the effectiveness of red propolis extract (RPE), calcium sodium phosphosilicate (Novamin) and arginine-calcium carbonate (ACC) in occluding dentine tubules.
  6. Chua EG, Parolia A, Ahlawat P, Pau A, Amalraj FD
    BMC Oral Health, 2014;14:53.
    PMID: 24886335 DOI: 10.1186/1472-6831-14-53
    To investigate the antifungal activity of propolis, triple antibiotic paste (TAP), 2% chlorhexidine gel and calcium hydroxide with propylene glycol on Candida albicans-infected root canal dentinal tubules at two different depths (200 μm and 400 μm) and two time intervals (day 1 and 7).
  7. Parolia A, Adhauliya N, de Moraes Porto IC, Mala K
    Oral Health Dent Manag, 2014 Mar;13(1):120-6.
    PMID: 24603928
    To evaluate and compare microleakage around class V cavities restored with silorane and dimethacrylate-based composite resins.
  8. Tan JM, Parolia A, Pau AK
    BMC Oral Health, 2013;13:52.
    PMID: 24098931 DOI: 10.1186/1472-6831-13-52
    This study compared the effectiveness of a Specially Designed Paste Carrier technique with the Syringe-Spreader technique and the Syringe-Lentulo spiral technique in the intracanal placement of calcium hydroxide.
  9. Jacob A, Parolia A, Pau A, Davamani Amalraj F
    PMID: 26303848 DOI: 10.1186/s12906-015-0814-1
    To evaluate and compare the effects of ethanolic extracts of Malaysian propolis and Brazilian red propolis at different concentrations on the migration and proliferation of fibroblast cells.
  10. Jhajharia K, Parolia A, Shetty KV, Mehta LK
    J Int Soc Prev Community Dent, 2015 Jan-Feb;5(1):1-12.
    PMID: 25767760 DOI: 10.4103/2231-0762.151956
    Endodontic disease is a biofilm-mediated infection, and primary aim in the management of endodontic disease is the elimination of bacterial biofilm from the root canal system. The most common endodontic infection is caused by the surface-associated growth of microorganisms. It is important to apply the biofilm concept to endodontic microbiology to understand the pathogenic potential of the root canal microbiota as well as to form the basis for new approaches for disinfection. It is foremost to understand how the biofilm formed by root canal bacteria resists endodontic treatment measures. Bacterial etiology has been confirmed for common oral diseases such as caries and periodontal and endodontic infections. Bacteria causing these diseases are organized in biofilm structures, which are complex microbial communities composed of a great variety of bacteria with different ecological requirements and pathogenic potential. The biofilm community not only gives bacteria effective protection against the host's defense system but also makes them more resistant to a variety of disinfecting agents used as oral hygiene products or in the treatment of infections. Successful treatment of these diseases depends on biofilm removal as well as effective killing of biofilm bacteria. So, the fundamental to maintain oral health and prevent dental caries, gingivitis, and periodontitis is to control the oral biofilms. From these aspects, the formation of biofilms carries particular clinical significance because not only host defense mechanisms but also therapeutic efforts including chemical and mechanical antimicrobial treatment measures have the most difficult task of dealing with organisms that are gathered in a biofilm. The aim of this article was to review the mechanisms of biofilms' formation, their roles in pulpal and periapical pathosis, the different types of biofilms, the factors influencing biofilm formation, the mechanisms of their antimicrobial resistance, techniques to identify biofilms.
  11. Parolia A, Kumar H, Ramamurthy S, Davamani F, Pau A
    BMC Oral Health, 2020 11 25;20(1):339.
    PMID: 33238961 DOI: 10.1186/s12903-020-01330-0
    BACKGROUND: The successful outcome of endodontic treatment depends on controlling the intra-radicular microbial biofilm by effective instrumentation and disinfection using various irrigants and intracanal medicaments. Instrumentation alone cannot effectively debride the root canals specially due to the complex morphology of the root canal system. A number of antibiotics and surfactants are being widely used in the treatment of biofilms however, the current trend is towards identification of natural products in disinfection. The aim of the study was to determine the antibacterial effect of chitosan-propolis nanoparticle (CPN) as an intracanal medicament against Enterococcus faecalis biofilm in root canal.

    METHODS: 240 extracted human teeth were sectioned to obtain 6 mm of the middle third of the root. The root canal was enlarged to an internal diameter of 0.9 mm. The specimens were inoculated with E. faecalis for 21 days. Following this, specimens were randomly divided into eight groups (n = 30) according to the intracanal medicament placed: group I: saline, group II: chitosan, group III: propolis100 µg/ml (P100), group IV: propolis 250 µg/ml (P250), group V: chitosan-propolis nanoparticle 100 µg/ml (CPN100), group VI: chitosan-propolis nanoparticle 250 µg/ml (CPN250), group VII: calcium hydroxide(CH) and group VIII: 2% chlorhexidine (CHX) gel. Dentine shavings were collected at 200 and 400 μm depths, and total numbers of CFUs were determined at the end of day one, three and seven. The non-parametric Kruskal Wallis and Mann-Whitney tests were used to compare the differences in reduction of CFUs between all groups and probability values of p 

  12. Mohan M, Lin KH, Parolia A, Pau A
    Int J Dent, 2021;2021:4573459.
    PMID: 34608391 DOI: 10.1155/2021/4573459
    Objectives: The research aimed to investigate if emotional intelligence (EI) scores of dental undergraduates influenced their patients' satisfaction with the treatment received.

    Methods: A 33-item EI questionnaire was completed by 46 dental undergraduates in a cross-sectional study. Responses, measured on a five-point Likert scale, were summed to yield EI scores. Patients treated by the same undergraduates were invited to complete a patient satisfaction (PS) questionnaire. EI and PS scores were calculated and compared by undergraduates' gender and the patients' age and education status. The four EI factors (optimism/mood regulation, appraisal of emotions, utilization of emotions, and social skills of students) were correlated with PS using Spearman's correlation test with a significance level set at p < 0.05.

    Results: EI scores did not differ significantly between male (N = 23) and female (N = 23) undergraduates (p=0.218). PS was not associated with patients' gender, but those educated to the secondary school level were more likely to be satisfied compared to those educated to the college/university level (p=0.022). Of the four EI factors, optimism/mood regulation was positively correlated with PS (p=0.049).

    Conclusion: The results of the study suggest that the EI of the students can influence PS. Practical Implications. Interventions to enhance EI can be developed to improve the patient experience.

  13. Gupta S, Parolia A, Jain A, Kundabala M, Mohan M, de Moraes Porto IC
    J Indian Soc Pedod Prev Dent, 2015 Jul-Sep;33(3):245-9.
    PMID: 26156281 DOI: 10.4103/0970-4388.160402
    The aim of this in vitro study was an attempt to investigate the effect of different surface treatments on the bond strength between pre-existing composite and repair composite resin.
  14. Daood U, Parolia A, Matinlinna J, Yiu C, Ahmed HMA, Fawzy A
    Dent Mater, 2020 12;36(12):e386-e402.
    PMID: 33010944 DOI: 10.1016/j.dental.2020.09.008
    OBJECTIVES: Evaluate a new modified quaternary ammonium silane irrigant solution for its antimicrobial, cytotoxic and mechanical properties of dentine substrate.

    METHODS: Root canal preparation was performed using stainless steel K-files™ and F4 size protaper with irrigation protocols of 6% NaOCl + 2% CHX; 3.5% QIS; 2% QIS and sterile saline. Biofilms were prepared using E. faecalis adjusted and allowed to grow for 3 days, treated with irrigants, and allowed to grow for 7 days. AFM was performed and surface free energy calculated. MC3T3 cells were infected with endo irrigant treated E. faecalis biofilms. Raman spectroscopy of biofilms were performed after bacterial re-growth on root dentine and exposed to different irrigation protocols and collagen fibers analysed collagen fibers using TEM. Antimicrobial potency against E. faecalis biofilms and cytoxicity against 3T3 NIH cells were also. Resin penetration and MitoTracker green were also evaluated for sealer penetration and mitochondrial viability. Data were analysed using One-way ANOVA, principal component analysis and post-hoc Fisher's least-significant difference.

    RESULTS: Elastic moduli were maintained amongst control (5.5 ± 0.9) and 3.5% QIS (4.4 ± 1.1) specimens with surface free energy higher in QIS specimens. MC3T3 cells showed reduced viability in 6%NaOCl+2%CHX specimens compared to QIS specimens. DNA/purine were expressed in increased intensities in control and 6% NaOCl + 2% CHX specimens with bands around 480-490 cm-1 reduced in QIS specimens. 3.5% QIS specimens showed intact collagen fibrillar network and predominantly dead bacterial cells in confocal microscopy. 3.5% QIS irrigant formed a thin crust-type surface layer with cytoplasmic extensions of 3T3NIH spread over root dentine. Experiments confirmed MitoTracker accumulation in 3.5% treated cells.

    SIGNIFICANCE: Novel QIS root canal irrigant achieved optimum antimicrobial protection inside the root canals facilitating a toxic effect against the Enterococcus faecalis biofilm. Root dentine substrates exhibited optimum mechanical properties and there was viability of fibroblastic mitochondria.

  15. Pan JYY, Parolia A, Chuah SR, Bhatia S, Mutalik S, Pau A
    BMC Oral Health, 2019 01 14;19(1):14.
    PMID: 30642318 DOI: 10.1186/s12903-019-0710-z
    BACKGROUND: To determine the root canal morphology of human permanent maxillary and mandibular teeth in a Malaysian subpopulation using cone-beam computed tomography (CBCT).

    METHODS: A total of 208 CBCT images were examined retrospectively. Prevalence of an extra root/canal and internal morphology based on Vertucci's classification were observed in human maxillary and mandibular permanent teeth. Variations in the external and internal morphology were compared in relation to gender and tooth side (left vs right) using Pearson Chi-square and Fisher's exact tests with significance level set at p 

  16. Chia MSY, Parolia A, Lim BSH, Jayaraman J, Porto ICCM
    Restor Dent Endod, 2020 Aug;45(3):e28.
    PMID: 32839709 DOI: 10.5395/rde.2020.45.e28
    Objectives: To evaluate the outcome of in vitro studies comparing the effectiveness of QMix irrigant in removing the smear layer in the root canal system compared with other irrigants.

    Materials and Methods: The research question was developed by using Population, Intervention, Comparison, Outcome and Study design framework. Literature search was performed using 3 electronic databases PubMed, Scopus, and EBSCOhost until October 2019. Two reviewers were independently involved in the selection of the articles and data extraction process. Risk of bias of the studies was independently appraised using revised Cochrane Risk of Bias tool (RoB 2.0) based on 5 domains.

    Results: Thirteen studies fulfilled the selection criteria. The overall risk of bias was moderate. QMix was found to have better smear layer removal ability than mixture of tetracycline isonomer, an acid and a detergent (MTAD), sodium hypochlorite (NaOCl), and phytic acid. The efficacy was less effective than 7% maleic acid and 10% citric acid. No conclusive results could be drawn between QMix and 17% ethylenediaminetetraacetic acid due to conflicting results. QMix was more effective when used for 3 minutes than 1 minute.

    Conclusions: QMix has better smear layer removal ability compared to MTAD, NaOCl, Tubulicid Plus, and Phytic acid. In order to remove the smear layer more effectively with QMix, it is recommended to use it for a longer duration.

  17. Daood U, Aati S, Akram Z, Yee J, Yong C, Parolia A, et al.
    Biomater Sci, 2021 Jul 27;9(15):5344-5358.
    PMID: 34190236 DOI: 10.1039/d1bm00555c
    The aim of this study was to characterize multiscale interactions between high intensity focused ultrasound (HIFU) and dentin collagen and associated matrix-metalloproteinases, in addition to the analysis of the effect of HIFU on bacterial biofilms and biological properties. Dentin specimens were subjected to 5, 10 or 20 s HIFU. XPS spectra were acquired and TEM was performed on dentin slabs. Collagen orientation was performed using Raman spectroscopy. Calcium measurements in human dental pulpal cells (hDPCs) were carried out after 7 and 14 days. For macrophages, CD36+ and CD163+ were analysed. Biofilms were analyzed using CLSM. Tandem mass spectroscopy was performed for the detection of hydroxyproline sequences along with human MMP-2 quantification. Phosphorus, calcium, and nitrogen were detected in HIFU specimens. TEM images demonstrated the collagen network appearing to be fused together in the HIFU 10 and 20 s specimens. The band associated with 960 cm-1 corresponds to the stretching ν1 PO43-. The control specimens showed intensive calcium staining followed by HIFU 20 s > HIFU 10 s > HIFU 5 s specimens. Macrophages in the HIFU specimens co-expressed CD80+ and CD163+ cells. CLSM images showed the HIFU treatment inhibiting bacterial growth. SiteScore propensity determined the effect of HIFU on the binding site with a higher DScore representing better site exposure on MMPs. Multiscale mapping of dentin collagen after HIFU treatment showed no deleterious alterations on the organic structure of dentin.
  18. Daood U, Parolia A, Elkezza A, Yiu CK, Abbott P, Matinlinna JP, et al.
    Dent Mater, 2019 09;35(9):1264-1278.
    PMID: 31201019 DOI: 10.1016/j.dental.2019.05.020
    OBJECTIVE: To analyze effect of NaOCl+2% quaternary ammonium silane (QAS)-containing novel irrigant against bacteria impregnated inside the root canal system, and to evaluate its antimicrobial and mechanical potential of dentine substrate.

    METHODS: Root canal was prepared using stainless steel K-files™ and ProTaper™ and subjected to manual and ultrasonic irrigation using 6% NaOCl+2% CHX, 6% NaOCl+2% QAS and saline as control. For confocal-microscopy, Raman spectroscopy and SEM analysis before and after treatment, Enterococcus faecalis cultured for 7 days. Raman spectroscopy analysis was done across cut section of gutta percha/sealer-dentine to detect resin infiltration. Indentation of mechanical properties was evaluated using a Berkovich indenter. The contact angle of irrigants and surface free energy were evaluated. Mineralization nodules were detected through Alazarin red after 14 days.

    RESULTS: Control biofilms showed dense green colonies. Majority of E. faecalis bacteria were present in biofilm fluoresced red in NaOCl+2% QAS group. There was reduction of 484cm-1 Raman band and its intensity reached lowest with NaOCl+2% QAS. There was an increase in 1350-1420cm-1 intensity in the NaOCl+2% CHX groups. Gradual decrease in 1639cm-1 and 1609cm-1 Raman signal ratios were seen in the resin-depth region of 17μm>, 14.1μm> and 13.2μm for NaOCl+2% QAS, NaOCl+2% CHX and control groups respectively. All obturated groups showed an intact sealer/dentine interface with a few notable differences. 0.771 and 83.5% creep indentation distance for NaOCl+2% QAS ultrasonic groups were observed. Highest proportion of polar component was significantly found in the NaOCl+2% QAS groups which was significantly higher as compared to other groups. Mineralized nodules were increased in NaOCl+2% QAS.

    SIGNIFICANCE: Favorable antimicrobial and endodontic profile of the NaOCl+2% QAS solution might suggest clinical use for it for more predictable reduction of intracanal bacteria.

  19. Lim BSH, Parolia A, Chia MSY, Jayaraman J, Nagendrababu V
    Restor Dent Endod, 2020 May;45(2):e23.
    PMID: 32483540 DOI: 10.5395/rde.2020.45.e23
    Objectives: This study aimed to summarize the outcome of in vitro studies comparing the antibacterial effectiveness of QMix with other irrigants against Enterococcus faecalis.

    Materials and Methods: The research question was developed by using population, intervention, comparison, outcome, and study design framework. The literature search was performed using 3 electronic databases: PubMed, Scopus, and EBSCOhost until October 2019. The additional hand search was performed from the reference list of the eligible studies. The risk of bias of the studies was independently appraised using the revised Cochrane Risk of Bias tool (RoB 2.0).

    Results: Fourteen studies were included in this systematic review. The overall risk of bias for the selected studies was moderate. QMix was found to have a higher antimicrobial activity compared to 2% sodium hypochlorite (NaOCl), 17% ethylenediaminetetraacetic acid (EDTA), 2% chlorhexidine (CHX), mixture of tetracycline isonomer, an acid and a detergent (MTAD), 0.2% Cetrimide, SilverSol/H2O2, HYBENX, and grape seed extract (GSE). QMix had higher antibacterial efficacy compared to NaOCl, only when used for a longer time (10 minutes) and with higher volume (above 3 mL).

    Conclusions: QMix has higher antibacterial activity than 17% EDTA, 2% CHX, MTAD, 0.2% Cetrimide, SilverSol/H2O2, HYBENX, GSE and NaOCl with lower concentration. To improve the effectiveness, QMix is to use for a longer time and at a higher volume.

    Trial Registration: PROSPERO International prospective register of systematic reviews Identifier: CRD42018096763.

  20. Kan CY, H'ng JX, Goh A, Smales F, Tan EL, Zhang S, et al.
    Int Dent J, 2023 Feb;73(1):63-70.
    PMID: 35725589 DOI: 10.1016/j.identj.2022.04.011
    OBJECTIVE: This study aimed to evaluate the effect of methanol (70% v/v), ethanol (80% v/v), dimethyl sulfoxide (DMSO; 100% v/v) extracts of ginger rhizome (GR), and 6-shogaol on the pilocarpine-stimulated salivary flow rate in C57BL/6 mice.

    METHODS: Three extracts of ginger (Zingiber officinale) rhizome prepared by maceration using the respective solvents and 6-shogoal were reconstituted in normal saline with 0.2% DMSO. Thirty C57BL/6 15-week-old mice were divided into 5 groups: Group 1, saline; Group 2, 70% methanol extract; Group 3, 80% ethanol extract; Group 4, 100% DMSO extract; and Group 5, 6-shogaol. The baseline pilocarpine-stimulated salivary flow rate was measured at the age of 15 weeks (15th week), and treatment solutions were administered by intraperitoneal injection from the 16th to 18th week. The stimulated salivary flow rate during treatment weeks was recorded for each group, and its difference with baseline was analysed using paired-sample t test. The change in salivary flow rate between the treatment groups and the control group was analysed using one-way analysis of variance.

    RESULTS: Groups 2, 3, 4, and 5 showed a significant increase in salivary flow rate when compared to baseline (P < .05). The increase in salivary flow rate in all 4 treatment groups was significant when compared to the control group (P < .05). Group 4 produced the highest increase in salivary flow rate; however, the differences amongst the treatment groups did not reach statistical significance (P > .05).

    CONCLUSIONS: All GR extracts (70% methanol, 80% ethanol, 100% DMSO) and 6-shogaol were equally effective in increasing the pilocarpine-stimulated salivary flow rate in C57BL/6 mice when administered systemically as a sustained dose for 3 weeks.

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