Arginine and sodium fluoride affect the microbial composition and reduce biofilm metabolism and enamel mineral loss in an oral microcosm model.

OBJECTIVE: To assess the effects of arginine, with or without sodium fluoride (NaF; 1,450 ppm), on saliva-derived microcosm biofilms and enamel demineralization. METHODS: Saliva-derived biofilms were grown on bovine enamel blocks in 0.2 % sucrose-containing modified McBain medium, according to six experimental groups: control (McBain 0.2 %); 2.5 % arginine; 8 % arginine; NaF; 2.5 % arginine with NaF; and 8 % arginine with NaF. After 5 days of growth, biofilm viability was assessed by colony-forming units counting, laser scanning confocal microscopy was used to determine biofilm vitality and extracellular polysaccharide (EPS) production, while biofilm metabolism was evaluated using the resazurin assay and lactic acid quantification. Demineralization was evaluated by measuring pH in the culture medium and calcium release. Data were analyzed by Kruskal-Wallis' and Dunn's tests (p < 0.05). RESULTS: 8 % arginine with NaF showed the strongest reduction in total streptococci and total microorganism counts, with no significant difference compared to arginine without NaF. Neither 2.5 % arginine alone nor NaF alone significantly reduced microbial counts compared to the control, although in combination, a reduction in all microbial groups was observed. Similar trends were found for biofilm vitality and EPS, and calcium released to the growth medium. CONCLUSIONS: 8 % Arginine, with or without NaF, exhibited the strongest antimicrobial activity and reduced enamel calcium loss. Also, NaF enhanced the effects of 2.5 % arginine, yielding similar results to 8 % arginine for most parameters analyzed. CLINICAL SIGNIFICANCE: The results provided further evidence on how arginine, with or without NaF, affects oral microcosm biofilms and enamel mineral loss.

Preventive dental erosion with silver diamine fluoride: An in vitro study.

OBJECTIVES: To evaluate the erosion preventive effect of 38 % silver diamine fluoride (SDF) solution in enamel and dentin of human permanent teeth. METHODS: Ninety enamel and ninety dentin blocks were prepared from permanent molars and allocated into three groups. Gp-SDF received a one-off application of 38 % SDF solution. Gp-SNF received a one-off application of a solution containing 800 ppm stannous chloride and 500 ppm fluoride. Gp-DW received a one-off application of deionized water. The blocks were submitted to acid challenge at pH 3.2, 2 min, 5 times/day for 7 days. All blocks were immersed in human saliva between cycles for one hour. The crystal characteristics, percentage of surface microhardness loss (%SMHL), surface loss, and elemental analysis and surface morphology were examined by X-ray diffraction (XRD), microhardness test, non-contact profilometry, and energy-dispersive X-ray spectroscopy (EDS) and scanning electron microscopy (SEM), respectively. Data of%SMHL and surface loss were analyzed by one-way ANOVA. RESULTS: XRD spectra revealed that fluorapatite and silver compounds formed in Gp-SDF, while fluorapatite and stannous compounds formed in Gp-SNF. Gp-DW presented only hydroxyapatite. The median (interquartile range) of%SMHL in Gp-SDF, Gp-SNF and Gp-DW were 27.86(3.66), 43.41(2.45), and 46.40(3.54) in enamel (p< 0.001), and 14.21(1.57), 27.99(1.95), and 33.18(1.73) in dentin, respectively (p < 0.001). The mean (standard deviation, µm) of surface loss of Gp-SDF, Gp-SNF, and Gp-DW were 2.81(0.59), 4.28(0.67), and 4.63(0.64) in enamel (p < 0.001) and 4.13(0.69), 6.04(0.61), and 7.72(0.66) in dentin, respectively (p < 0.001). SEM images exhibited less enamel corruption and more dentinal tubular occlusion in Gp-SDF compared to Gp-SNF and Gp-DW. EDS analysis showed silver was detected in Gp-SDF while stannous was detected in the dentin block of Gp-SNF. CONCLUSION: 38 % SDF yielded superior results in protecting enamel and dentin blocks from dental erosion compared to SNF and DW. CLINICAL SIGNIFICANCE: Topical application of 38 % SDF is effective in preventing dental erosion in human enamel and dentin.

Investigation of the impact of commonly used medications on the oral microbiome of individuals living without major chronic conditions.

BACKGROUND: Commonly used medications produce changes in the gut microbiota, however, the impact of these medications on the composition of the oral microbiota is understudied. METHODS: Saliva samples were obtained from 846 females and 368 males aged 35-69 years from a Canadian population cohort, the Atlantic Partnership for Tomorrow's Health (PATH). Samples were analyzed by 16S rRNA gene sequencing and differences in microbial community compositions between nonusers, single-, and multi-drug users as well as the 3 most commonly used medications (thyroid hormones, statins, and proton pump inhibitors (PPI)) were examined. RESULTS: Twenty-six percent of participants were taking 1 medication and 21% were reported taking 2 or more medications. Alpha diversity indices of Shannon diversity, Evenness, Richness, and Faith's phylogenetic diversity were similar among groups, likewise beta diversity as measured by Bray-Curtis dissimilarity (R2 = 0.0029, P = 0.053) and weighted UniFrac distances (R2 = 0.0028, P = 0.161) were non-significant although close to our alpha value threshold (P = 0.05). After controlling for covariates (sex, age, BMI), six genera (Saprospiraceae uncultured, Bacillus, Johnsonella, Actinobacillus, Stenotrophomonas, and Mycoplasma) were significantly different from non-medication users. Thyroid hormones, HMG-CoA reductase inhibitors (statins) and PPI were the most reported medications. Shannon diversity differed significantly among those taking no medication and those taking only thyroid hormones, however, there were no significant difference in other measures of alpha- or beta diversity with single thyroid hormone, statin, or PPI use. Compared to participants taking no medications, the relative abundance of eight genera differed significantly in participants taking thyroid hormones, six genera differed in participants taking statins, and no significant differences were observed with participants taking PPI. CONCLUSION: The results from this study show negligible effect of commonly used medications on microbial diversity and small differences in the relative abundance of specific taxa, suggesting a minimal influence of commonly used medication on the salivary microbiome of individuals living without major chronic conditions.

Effects of cigarette smoking on the growth of Streptococcus mutans biofilms: An in vitro study.

The increased incidence of dental caries by cigarette smoking (CS) has been widely reported in epidemiological studies, but the relationship between CS and cariogenic biofilm growth has been rarely studied. This study aims to investigate the effects of CS exposure on the growth and virulence of Streptococcus mutans biofilms (S. mutans). Briefly, S. mutans biofilms were formed on saliva-coated hydroxyapatite disks, which were exposed to CS 1, 3, and 6 times per day, respectively. In addition, S. mutans biofilms without CS exposure were considered as the control group. Acidogenicity, dry weight, colony-forming units (CFUs), water-soluble/insoluble extracellular polysaccharides (EPSs), and intracellular polysaccharides (IPSs) were analyzed and confocal laser scanning microscopy (CLSM) images of 74-h-old S. mutans biofilms were obtained. The lowest accumulation of biofilms and EPSs were detected in the 6 times/day CS exposure group compared with those of the control group and other CS exposure groups in 74-h-old S. mutans biofilms. CLSM also revealed the lowest bacterial count (live and dead cells) and EPSs biovolume in the six times/day CS exposure group in 74-h-old S. mutans biofilms. CS exposure inhibited the growth of S. mutans biofilm in vitro study, the anti-cariogenic biofilm formation was enhanced with a dose (frequency)-dependent at which frequency has more influence in the present findings.

Inflammatory phenotype modulation in the respiratory tract and systemic circulation of e-cigarette users: a pilot study.

Over 40 million people use e-cigarettes worldwide, but the impact of chronic e-cigarette use on health has not been adequately defined. In particular, effects of e-cigarette aerosol inhalation on inflammation and host defenses across the body are not fully understood. We conducted a longitudinal cohort pilot study to explore changes in the inflammatory state and monocyte function of e-cigarette users (n = 20) versus healthy controls (n = 13) and to evaluate effects of e-cigarette use reduction on the same. Saliva, sputum, and blood were obtained from e-cigarette users at baseline and after a 2-wk intervention of decreased e-cigarette use. Overall, across 38 proteins quantified by multiplex, airway samples from e-cigarette users tended to have decreased levels of immunomodulatory proteins relative to healthy controls, whereas levels of cytokines, chemokines, and growth factors in the circulation tended to be elevated. Specifically, e-cigarette users had lower levels of IL-1 receptor antagonist (IL-1Ra) in saliva (P < 0.0001), with higher IL-1Ra and growth-regulated oncogene (GRO) levels in sputum (P < 0.01 and P < 0.05, respectively), and higher levels of both TNFß (P < 0.0001) and VEGF (P < 0.0001) in plasma. Circulating monocytes from e-cigarette users had alterations in their inflammatory phenotype in response to reduced e-cigarette use, with blunted IL-8 and IL-6 release upon challenge with bacterial lipopolysaccharide (P < 0.001 and P < 0.05, respectively), suggesting a decreased ability to appropriately respond to bacterial infection. Based on these findings, chronic inhalation of e-cigarette aerosols alters the inflammatory state of the airways and systemic circulation, raising concern for the development of both inflammatory and infectious diseases in chronic users of e-cigarettes.

A comparative study based on activity, conformation and computational analysis on the inhibition of human salivary aldehyde dehydrogenase by phthalate plasticizers: Implications in assessing the safety of packaged food items.

Phthalate plasticizers are commonly used in various consumer-end products. Human salivary aldehyde dehydrogenase (hsALDH) is a detoxifying enzyme which defends us from the toxic aldehydes. Here, the effect of phthalates [Di-2-ethylhexyl phthalate (DEHP), Diethyl phthalate (DEP) and Dibutyl phthalate (DBP)] on hsALDH has been investigated. These plasticizers inhibited hsALDH, and the IC50 values were 0.48 ± 0.04, 283.20 ± 0.09 and 285.00 ± 0.14 µM for DEHP, DEP and DBP, respectively. DEHP was the most potent inhibitor among the three plasticizers. They exhibited mixed-type linear inhibition with inclination towards competitive-non-competitive inhibition. They induced both tertiary and secondary structural changes in the enzyme. Quenching of intrinsic hsALDH fluorescence in a constant manner was observed with a binding constant (Kb) of 8.91 × 106, 2.80 × 104, and 1.31 × 105 M-1, for DEHP, DEP and DBP, respectively. Computational analysis showed that these plasticizers bind stably in the proximity of hsALDH catalytic site, reciprocating via non-covalent interactions with some of the amino acids which are evolutionary conserved. Therefore, exposure to these plasticizers inhibits hsALDH which increases the risk of aldehyde induced toxicity, adversely affecting oral health. The study has implications in assessing the safety of packaged food items which utilize phthalates.

Blending oxytocin and dopamine with everyday creativity.

Converging evidence suggests that oxytocin (OT) is associated with creative thinking (CT) and that release of OT depends on ADP ribosyl-cyclases (CD38 and CD157). Neural mechanisms of CT and OT show a strong association with dopaminergic (DA) pathways, yet the link between CT and CD38, CD157, dopamine receptor D2 (DRD2) and catechol-O-methyltransferase (COMT) peripheral gene expression remain inconclusive, thus limiting our understanding of the neurobiology of CT. To address this issue, two principal domains of CT, divergent thinking (AUT), were assessed. In men, both AUT is associated with gene expression of CD38, CD157, and their interaction CD38 × CD157. There were no significant associations for DA expression (DRD2, COMT, DRD2 × COMT) on both CT measures. However, analysis of the interactions of OT and DA systems reveal significant interactions for AUT in men. The full model explained a sizable 39% of the variance in females for the total CT score. The current findings suggest that OT and DA gene expression contributed significantly to cognition and CT phenotype. This provides the first empirical foundation of a more refined understanding of the molecular landscape of CT.

Nivolumab-Related Dry Mouth and Dry Eye: Cross-Sectional Study.

To evaluate ICIs related dry eye and dry mouth in nivolumab therapy, 24 patients receiving nivolumab (group 1), 30 patients in remission without treatment for 6 months (group 2), 30 healthy participants (group 3) were cross-sectionally examined. Schirmer's 1, 2, TSH blood tests, serological analysis, salivary flow scintigraphy and minor-salivary gland biopsy were performed. Schirmer's tests were performed with anesthetic (1) and without anesthetic (2). Schirmer's scores were lower in group 1 with more frequent reduced tear production (p < 0.001). TSH levels negatively correlated with Schirmer's scores. Functional insufficiency was detected by salivary flow scintigraphy in 7 out of 10 patients with Schirmer's test positivity. In Schirmer's positive patients, lymphocytic sialadenitis was confirmed in 4 patients (focus score > 1) and CD4 T lymphocyte precipitation was observed in 6 patients. Nivolumab therapy may be associated with ICIs related immune sicca.

Treatment of periodontal diseases by the local drug delivery system using 1% chlorhexidine gel: A randomized clinical trial.

The idea of the local drug delivery system is getting popular nowadays to treat gingivitis and periodontitis. The method of delivering the drug locally is quite easy and requires minimal intervention. This delivery system not only treats the periodontal diseases effectively but also prevents the side effects linked with the use of the drugs which are used orally for longer periods to cure these diseases. Chlorhexidine (CHX) is being widely used to treat these conditions because of its broad spectrum anti-bacterial effect and is found to be more effective in lowering plaque formation. The aim of this study was to appraise the effect of the local drug delivery system by using 1% CHX gel in patients with periodontal diseases. 1% CHX gel was prepared and its physicochemical characteristics were then assessed. Clinical parameters and inflammatory salivary biomarkers were evaluated in two groups of patients. Group I: standard treatment group. Group II: gel treatment group. These parameters were evaluated before treatment and after 4 weeks of treatment. 1% CHX gel was highly effective in reducing gingivitis and periodontitis by using the local drug delivery system which allowed the drug to retain into the periodontal pocket for prolong period of time.

Inactivation of SARS-CoV-2 virus in saliva using a guanidium based transport medium suitable for RT-PCR diagnostic assays.

BACKGROUND: Upper respiratory samples used to test for SARS-CoV-2 virus may be infectious and present a hazard during transport and testing. A buffer with the ability to inactivate SARS-CoV-2 at the time of sample collection could simplify and expand testing for COVID-19 to non-conventional settings. METHODS: We evaluated a guanidium thiocyanate-based buffer, eNAT™ (Copan) as a possible transport and inactivation medium for downstream Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) testing to detect SARS-CoV-2. Inactivation of SARS-CoV-2 USA-WA1/2020 in eNAT and in diluted saliva was studied at different incubation times. The stability of viral RNA in eNAT was also evaluated for up to 7 days at room temperature (28°C), refrigerated conditions (4°C) and at 35°C. RESULTS: SARS-COV-2 virus spiked directly in eNAT could be inactivated at >5.6 log10 PFU/ml within a minute of incubation. When saliva was diluted 1:1 in eNAT, no cytopathic effect (CPE) on VeroE6 cells was observed, although SARS-CoV-2 RNA could be detected even after 30 min incubation and after two cell culture passages. A 1:2 (saliva:eNAT) dilution abrogated both CPE and detectable viral RNA after as little as 5 min incubation in eNAT. SARS-CoV-2 RNA from virus spiked at 5X the limit of detection remained positive up to 7 days of incubation in all tested conditions. CONCLUSION: eNAT and similar guanidinium thiocyanate-based media may be of value for transport, stabilization, and processing of clinical samples for RT-PCR based SARS-CoV-2 detection.

The cAMP-phosphodiesterase 4 (PDE4) controls ß-adrenoceptor- and CFTR-dependent saliva secretion in mice.

Saliva, while often taken for granted, is indispensable for oral health and overall well-being, as inferred from the significant impairments suffered by patients with salivary gland dysfunction. Here, we show that treatment with several structurally distinct PAN-PDE4 inhibitors, but not a PDE3 inhibitor, induces saliva secretion in mice, indicating it is a class-effect of PDE4 inhibitors. In anesthetized mice, while neuronal regulations are suppressed, PDE4 inhibition potentiates a ß-adrenoceptor-induced salivation, that is ablated by the ß-blocker Propranolol and is absent from homozygous ΔF508-CFTR mice lacking functional CFTR. These data suggest that PDE4 acts within salivary glands to gate saliva secretion that is contingent upon the cAMP/PKA-dependent activation of CFTR. Indeed, PDE4 contributes the majority of total cAMP-hydrolytic capacity in submandibular-, sublingual-, and parotid glands, the three major salivary glands of the mouse. In awake mice, PDE4 inhibitor-induced salivation is reduced by CFTR deficiency or ß-blockers, but also by the muscarinic blocker Atropine, suggesting an additional, central/neuronal mechanism of PDE4 inhibitor action. The PDE4 family comprises four subtypes, PDE4A-D. Ablation of PDE4D, but not PDE4A-C, produced a minor effect on saliva secretion, implying that while PDE4D may play a predominant role, PDE4 inhibitor-induced salivation results from the concurrent inactivation of multiple (at least two) PDE4 subtypes. Taken together, our data reveal a critical role for PDE4/PDE4D in controlling CFTR function in an in vivo model and in inducing salivation, hinting at a therapeutic potential of PDE4 inhibition for cystic fibrosis and conditions associated with xerostomia.

Evaluation of Anti-Biofilm Activity of Mouthrinses Containing Tannic Acid or Chitosan on Dentin In Situ.

In contrast to enamel, dentin surfaces have been rarely used as substrates for studies evaluating the effects of experimental rinsing solutions on oral biofilm formation. The aim of the present in situ study was to investigate the effects of tannic acid and chitosan on 48-h biofilm formation on dentin surfaces. Biofilm was formed intraorally on dentin specimens, while six subjects rinsed with experimental solutions containing tannic acid, chitosan and water as negative or chlorhexidine as positive control. After 48 h of biofilm formation, specimens were evaluated for biofilm coverage and for viability of bacteria by fluorescence and scanning electron microscopy. In addition, saliva samples were collected after rinsing and analyzed by fluorescence (five subjects) and transmission electron microscopy (two subjects) in order to investigate the antibacterial effect on bacteria in a planktonic state and to visualize effects of the rinsing agents on salivary proteins. After rinsing with water, dentin specimens were covered by a multiple-layered biofilm with predominantly vital bacteria. In contrast, chlorhexidine led to dentin surfaces covered only by few and avital bacteria. By rinsing with tannic acid both strong anti-adherent and antibacterial effects were observed, but the effects declined in a time-dependent manner. Transmission electron micrographs of salivary samples indicated that aggregation of proteins and bacteria might explain the antiadhesion effects of tannic acid. Chitosan showed antibacterial effects on bacteria in saliva, while biofilm viability was only slightly reduced and no effects on bacterial adherence on dentin were observed, despite proteins being aggregated in saliva after rinsing with chitosan. Tannic acid is a promising anti-biofilm agent even on dentin surfaces, while rinsing with chitosan could not sufficiently prevent biofilm formation on dentin.

The Effect of Melatonin on Periodontitis.

BACKGROUND: Periodontitis is a chronic disease with a complex etiology that includes bacterial colonization, excessive inflammation, and oxidative stress. The hormone melatonin has antioxidant properties and might contribute to alleviating chronic conditions by reducing oxidative stress. The aim of this study was to analyze the effect of exogenous melatonin on periodontitis in an animal model of the disease as well as in patients with periodontitis. METHODS: In rats with ligature-induced periodontitis, melatonin was administered in drinking water for two weeks. In the human study, patients with treatment-resistant periodontitis were asked to rinse their mouths with a solution containing melatonin or placebo every evening for two weeks. Periodontal status as well as salivary markers of oxidative stress were assessed at the end of the study. RESULTS: Neither radiography nor µCT revealed any significant effects of melatonin on alveolar bone loss. Gum recession was the only improved macroscopic measure in rats (p < 0.05). Analysis of salivary markers of oxidative stress revealed no effects of treatment in rats or humans despite clearly elevated melatonin concentrations in melatonin treated groups. CONCLUSION: Our results do not support the use of melatonin for the treatment of periodontitis. However, the negative outcome is limited by the short duration of the study and the chosen route of application as well as the dose of melatonin.

A concerted probiotic activity to inhibit periodontitis-associated bacteria.

Periodontitis can result in tooth loss and the associated chronic inflammation can provoke several severe systemic health risks. Adjunctive to mechanical treatment of periodontitis and as alternatives to antibiotics, the use of probiotic bacteria was suggested. In this study, the inhibitory effect of the probiotic Streptococcus salivarius subsp. salivarius strains M18 and K12, Streptococcus oralis subsp. dentisani 7746, and Lactobacillus reuteri ATCC PTA 5289 on anaerobic periodontal bacteria and Aggregatibacter actinomycetemcomitans was tested. Rarely included in other studies, we also quantified the inverse effect of pathogens on probiotic growth. Probiotics and periodontal pathogens were co-incubated anaerobically in a mixture of autoclaved saliva and brain heart infusion broth. The resulting genome numbers of the pathogens and of the probiotics were measured by quantitative real-time PCR. Mixtures of the streptococcal probiotics were also used to determine their synergistic, additive, or antagonistic effects. The overall best inhibitor of the periodontal pathogens was L. reuteri ATCC PTA 5289, but the effect is coenzyme B12-, anaerobiosis-, as well as glycerol-dependent, and further modulated by L. reuteri strain DSM 17938. Notably, in absence of glycerol, the pathogen-inhibitory effect could even turn into a growth spurt. Among the streptococci tested, S. salivarius M18 had the most constant inhibitory potential against all pathogens, followed by K12 and S. dentisani 7746, with the latter still having significant inhibitory effects on P. intermedia and A. actinomycetemcomitans. Overall, mixtures of the streptococcal probiotics did inhibit the growth of the pathogens equally or-in the case of A. actinomycetemcomitans- better than the individual strains. P. gingivalis and F. nucleatum were best inhibited by pure cultures of S. salivarius K12 or S. salivarius M18, respectively. Testing inverse effects, the growth of S. salivarius M18 was enhanced when incubated with the periodontal pathogens minus/plus other probiotics. In contrast, S. oralis subsp. dentisani 7746 was not much influenced by the pathogens. Instead, it was significantly inhibited by the presence of other streptococcal probiotics. In conclusion, despite some natural limits such as persistence, the full potential for probiotic treatment is by far not utilized yet. Especially, further exploring concerted activity by combining synergistic strains, together with the application of oral prebiotics and essential supplements and conditions, is mandatory.

Transitions in oral and gut microbiome of HPV+ oropharyngeal squamous cell carcinoma following definitive chemoradiotherapy (ROMA LA-OPSCC study).

BACKGROUND: Oral and gut microbiomes have emerged as potential biomarkers in cancer. We characterised the oral and gut microbiomes in a prospective observational cohort of HPV+ oropharyngeal squamous cell carcinoma (OPSCC) patients and evaluated the impact of chemoradiotherapy (CRT). METHODS: Saliva, oropharyngeal swabs over the tumour site and stool were collected at baseline and post-CRT. 16S RNA and shotgun metagenomic sequencing were used to generate taxonomic profiles, including relative abundance (RA), bacterial density, α-diversity and ß-diversity. RESULTS: A total of 132 samples from 22 patients were analysed. Baseline saliva and swabs had similar taxonomic composition (R2 = 0.006; p = 0.827). Oropharyngeal swabs and stool taxonomic composition varied significantly by stage, with increased oral RA of Fusobacterium nucleatum observed in stage III disease (p < 0.05). CRT significantly reduced the species richness and increased the RA of gut-associated taxa in oropharyngeal swabs (p < 0.05), while it had no effect in stool samples. These findings remained significant when adjusted by stage, smoking status and antibiotic use. CONCLUSIONS: Baseline oral and gut microbiomes differ by stage in this HPV+ cohort. CRT caused a shift towards a gut-like microbiome composition in oropharyngeal swabs. Stage-specific features and the transitions in oral microbiome might have prognostic and therapeutic implications.

Comparison of salivary total protein and electrolyte profile in HIV patients with and without antiretroviral therapy.

BACKGROUND: Saliva provides a primary defense mechanism against several infectious diseases through its numerous immunological and non-immunological factors. Alteration in the composition of saliva often compromises its defense mechanisms, predisposing the oral cavity to disease entities. HIV patients under antiretroviral therapy (ART) have shown to exhibit altered salivary composition. These changes are postulated to be a result of the effect of ART on the salivary protein and electrolytes levels. OBJECTIVES: The present study aims to assess the potential difference in the salivary total protein and electrolyte levels in HIV patients with and without ART. METHODS: Patients were divided into 3 groups- Group A (HIV-1 positive patient under ART for at least 6 months)-66, Group B (HIV-1 positive patient not started on ART)-66, Group C (HIV negative patients)-66. Saliva samples were collected and evaluated for total salivary protein and electrolyte levels in all the 3 groups. RESULTS: There was a statistically significant difference in the salivary protein (p = 0.000) and electrolyte (Sodium, p = 0.000; Potassium, p = 0.039; chlorine, p = 0.027; ionized calcium, p = 0.002) levels among the three groups. CONCLUSION: HIV positive individuals with and without ART have alteration in the salivary composition. Some of these alterations (total protein and iCa levels) are due to the HIV infection, while others (Na, K, Cl) could be due to ART or a combined effect of both. Salivary changes in HIV positive individuals could predispose them to oral diseases. Thus, regular oral examination and prophylactic regimen must be formulated to maintain their oral hygiene and quality of life.

The impact of medical cannabis consumption on the oral flora and saliva.

OBJECTIVE: To evaluate the effect of medical cannabis consumption on oral flora and saliva. DESIGN: A clinical prospective study, at the rheumatology clinic of the Nazareth Hospital in Nazareth, recruiting consecutively patients approved for medical cannabis, evaluating their saliva flow, pH and microbial load of Streptococcus mutans and Lactobacillus, prior to and under medical cannabis treatment. METHODS: Patients recently licensed for medical cannabis treatment, were recruited just prior to starting medical cannabis consumption (week 0), 1 and 4 weeks later, patients provided 5-minute time saliva samples, which were measured for their volume and pH, and cultured on a special microbial kit, evaluating the growth of Streptococcus mutans and Lactobacillus. RESULTS: Out of 16 patients enrolled, 14 were female and had fibromyalgia. The mean age of the patients was 52.8±12.9 years. The mean saliva flow at week 0, week 1 and week 4 were 5.38±3.36 ml/5-minutes, 6 (p = 0.769) and 5.45 (p = 0.391), respectively, and for saliva pH were 6.28, 5.94 (p = 0.51) and 5.5 (p = 0.07) respectively also. The mean Streptococcus mutans growth score at weeks 0, 1 and 4 was1.8±0.75, 1.6±0.83 (p = 0.234), and 2.4±0.84 (p = 0.058), respectively. The mean Lactobacilli growth score at weeks 0, 1 and 4 was 2.59±0.88, 3.1±0.69 (p = 0.033) and 3.3±0.67 (p = 0.025), respectively. CONCLUSIONS: The results of this study show that medical cannabis consumption has no significant effect on saliva volume or pH, but it may be associated with changes in salivary levels of oral microbes such as Streptococcus mutans and Lactobacilli.

Longitudinal saliva omics responses to immune perturbation: a case study.

Saliva omics has immense potential for non-invasive diagnostics, including monitoring very young or elderly populations, or individuals in remote locations. In this study, multiple saliva omics from an individual were monitored over three periods (100 timepoints) involving: (1) hourly sampling over 24 h without intervention, (2) hourly sampling over 24 h including immune system activation using the standard 23-valent pneumococcal polysaccharide vaccine, (3) daily sampling for 33 days profiling the post-vaccination response. At each timepoint total saliva transcriptome and proteome, and small RNA from salivary extracellular vesicles were profiled, including mRNA, miRNA, piRNA and bacterial RNA. The two 24-h periods were used in a paired analysis to remove daily variation and reveal vaccination responses. Over 18,000 omics longitudinal series had statistically significant temporal trends compared to a healthy baseline. Various immune response and regulation pathways were activated following vaccination, including interferon and cytokine signaling, and MHC antigen presentation. Immune response timeframes were concordant with innate and adaptive immunity development, and coincided with vaccination and reported fever. Overall, mRNA results appeared more specific and sensitive (timewise) to vaccination compared to other omics. The results suggest saliva omics can be consistently assessed for non-invasive personalized monitoring and immune response diagnostics.

Effect of Capsaicinoids on Neurophysiological, Biochemical, and Mechanical Parameters of Swallowing Function.

Oropharyngeal dysphagia is prevalent in age-related neurological disorders presenting with impaired efficacy and safety of swallowing due to a loss of muscle force and sensory deficits. Stimulating the oropharynx with capsaicin that mediates Substance P release is an emerging pharmacological treatment option which needs further scientific evidence. Our aim was to comprehensively evaluate the effect of capsaicin on biochemical, neurophysiological, and biomechanical parameters of swallowing function. In a randomized study on healthy individuals, the impact of orally administered capsaicinoids at different dosages and application durations in comparison to non-carbonated water was evaluated. Time course and magnitude of salivary Substance P increase were monitored. Magnetoencephalography was used to detect cortical swallowing network alterations. Modifications in swallowing biomechanics were measured applying high-resolution pharyngeal manometry. Capsaicinoids at 10 µmol/L improved swallowing efficacy as seen by a significant increase of pharyngeal contractile integral and upper esophageal sphincter activation and relaxation times in manometry. Significant improvement of precision in a challenging swallow task accompanied by a reduction in swallowing-related submental electromyographic power was observed with capsaicinoids preconditioning at 10 µmol/L over 5 min, but not with continuous stimulation. The cortical activation pattern remained unchanged after any intervention. A significant increase of salivary Substance P was not detected with 10 µmol/L but with 50 µmol/L and lasted for 15 min after application. Capsaicinoids mediate dose-dependent Substance P release and positively alter swallowing biomechanics in healthy subjects. The results provide supportive evidence for the value of natural capsaicinoids to improve swallowing function.

Neurochemical regulation of Aedes aegypti salivary gland function.

The salivary gland of hematophagous arthropods is critical for blood meal acquisition, blood vessel localization, and secretion of digestive enzymes. Thus, there is significant interest in the regulation of salivary gland function and mechanisms driving the secretion of saliva and digestive proteins. We aimed to gain a broader understanding of the regulatory role of aminergic, cholinergic, and octopaminergic neuromodulators to saliva and protein secretion from the female A. aegypti salivary gland. Quantification of saliva after injection with neuromodulators showed that dopamine, serotonin, and pilocarpine increased the secretory activity of the salivary gland with potency rankings dopamine = serotonin > pilocarpine. No change in saliva secretion was observed with octopamine or ergonovine, which indicates the A. aegypti salivary gland may be regulated by dopaminergic, serotonergic, and cholinergic systems, but are not likely regulated by octopaminergic or tryptaminergic systems. Next, we studied the regulatory control of dopamine-mediated salivation. Data indicate extracellular calcium flux, but not neural function, is critical for dopamine-mediated salivation, which suggests epithelial transport of ions and not neuronal control is responsible for dopamine-mediated salivation. For regulation of protein secretion, data indicate dopamine or serotonin exposure facilitates amylase secretion, whereas serotonin but not dopamine exposure increased apyrase concentrations in the secreted saliva. General immunoreactivity to anti-rat D1-dopamine receptor antibody was observed, yet immunoreactivity to the anti-rat D2-receptor antibody was identified in the proximal regions of the lateral lobes and slight immunoreactivity in the distal portion of the lateral lobe, with no expression in the medial lobe.