"The Standard Procedure" for Investigation of Oral Neutrophils in Oral Diseases.

Aim: There is need of an objective "standard procedure" that is reliable and clinically applicable for estimating oral neutrophil content in relation to oral diseases. Methods: Forty-one patients with suspected oral candidosis (OC) and nine healthy controls with no oral mucosal disease were flushing with 10 ml mouth rinse (MR) (sterile phosphate-buffered saline) for 1 min. Aliquots were stored on different conditions to explore stability, storage, and fixation conditions for analysis by flow cytometry. Results: The optimal storage and fixation condition for MR was by fixation 1 : 1 in 10% formalin and stored at 5°C. This procedure yielded stable results up to 7 days after collection. The ability of the optimized method to relate oral neutrophils to inflammation was demonstrated by the significantly higher number of neutrophils in patients with primary OC (p = 0.0334) compared to healthy controls. Conclusion: This method is rapid, reliable, and clinically applicable for establishing the content of oral neutrophils. We demonstrate increased density of oral neutrophils in the MR of patients with OC. The potential of the method is to be "the standard procedure" for investigation of the oral inflammation in patients with oral diseases as it is noninvasive and provides high stability, clinical relevance, and minimal handling.

Danish post-marketing pharmacosurveillance of spontaneous Oral Adverse Drug Reactions 2009-2019.

Post-marketing pharmacosurveillance is important to reduce harm to patients from marketed drugs. Oral adverse drug reactions (OADRs) are seldom reported and only few OADRs are listed scarcely in summary of product characteristics (SmPC) of drugs. OBJECTIVE: Structured search for OADRs in the Danish Medicines Agencies database from January 2009 to July 2019. RESULTS: Forty-eight percent of OADRs were categorized as "serious" where oro-facial swelling was reported 1041 times, medication-related osteonecrosis of the jaw (MRONJ) 607 times and para- or hypoaesthesia 329 times. Four-hundred-eighty OADRs in 343 cases were related to biologic or biosimilar drugs where 73% affected the jawbone as MRONJ. Physician reported 44%, dentists 19% and citizens 10% of OADRs. CONCLUSIONS: Health care professionals had a sporadic reporting pattern that seemed to be influenced by the debate in the community and in professional circles but also by the information in the SmPC of the drugs. The results indicate some reporting stimulation of OADRs in relation to Gardasil 4, Septanest, Eltroxin and MRONJ. Eventually the knowledge of OADRs increases but there is a risk of skewed information if reporting is not systematic, reliable and consistent. All healthcare professionals must be educated in spotting and reporting all suspected adverse drug reactions.

Lactobacillus rhamnosus strains of oral and vaginal origin show strong antifungal activity in vitro.

Background: Intake of probiotic bacteria may prevent oral Candida infection. Objective: To screen the antifungal activity of 14 Lactobacillus candidate strains of human origin, against six opportunistic C. albicans and non-albicans species. A second aim was to study the acid production of the four strains showing the strongest antifungal activity. Methods: We used an agar overlay growth inhibition assay to the assess the antifungal activity of the lactobacilli. The acid-producing capacity was measured with pH micro-sensors. Results: All 14 Lactobacillus candidates inhibited the growth of the Candida spp. The four best-performing strains were L. rhamnosus DSM 32992 (oral origin), L. rhamnosus DSM 32991 (oral), L. jensenii 22B42 (vaginal), and L. rhamnosus PB01 (vaginal). The difference between L. rhamnosus DSM 32992 and the other three strains was statistically significant (p < 0.001). The Candida spp. differed in susceptibility; C. parapsilosis was highly inhibited, while C. krusei was not or slightly inhibited. The oral L. rhamnosus DSM 32992 and DSM 32991 strains showed the lowest pH-values. Conclusion: Screening of probiotic lactobacilli showed significant strain-dependent variations in their antifungal capacity in a pH-dependent mode. Two strains of oral origin were most effective. A further characterization seems justified to elaborate on their probiotic properties.

Oral symptoms and pathologies in Danish patients with chronic kidney disease- a pilot study.

The aim was to investigate oral health in randomly selected patients with chronic kidney disease (CKD). Data obtained by structured interview (self-reported lifestyle, oral symptoms and regularity of dental visits) and oral examination of patients with CKD from the Copenhagen University Hospital. Fourteen patients with CKD were screened. Only half of the patients reported regular dental visits and poor dental status was registered in half of the patients. Oral mucosal changes were registered in thirteen patients (93%). Eleven patients (79%) had gingival inflammatory disease. Twelve patients (86%) were carriers of Candida, and three (21%) had oral candidosis. Six patients (43%) had low whole saliva flow rate. Twelve patients (86%) reported at least one oral symptom. Overall, there was no differences in oral symptoms or findings related to kidney transplanted or not transplanted patients. The small sample size most likely influences the results. However, the vast majority of patients with CKD reported oral symptoms and only half consulted a dentist regularly. Poor dental status, oral mucosal changes and gingival disease were prevalent findings. Patients with CKD need focus on daily oral healthcare and regular dental visits. Interdisciplinary cooperation could encourage patients with CKD to focus on oral health.

The oral microbiome in oral lichen planus during a 1-year randomized clinical trial.

BACKGROUND: Several recent studies have investigated the oral bacteriome in oral lichen planus (OLP), but longitudinal changes in microbiome have not been investigated. OBJECTIVE: To study the bacteriome and mycobiome in OLP over a 1-year period and the impact of topical treatment. MATERIAL AND METHODS: Samples from 22 symptomatic OLP patients from a double-blinded, randomized intervention study were collected over a 1-year course at five visits. Bacterial and fungal abundances were investigated through lesional cytobrush (CB) and full mouthwash (MW). Initially, all patients received conventional (antimycotic or steroid) and probiotic or placebo treatment. RESULTS: The microbial composition differed between the MW and CB samples. During the study period, the microbial composition was individual, with pronounced variability between visits. Patients grouped according to initial conventional treatment. During the study period, unidirectional change in the bacteriome was seen in the antimycotic group, whereas the mycobiome was stable. Malassezia restricta was the most abundant fungus. CONCLUSIONS: The microbial composition of MW and CB differs in OLP. CB composition is less influenced by conventional and probiotic intervention. Initial antimycotic treatment influenced the bacteriome during the 1-year period. How the oral microbiome in health and disease is influenced by individual variability of fungi and bacteria, and Malassezia needs further investigation.

Probiotic Lactobacillus reuteri has antifungal effects on oral Candida species in vitro.

Background: An alternative approach for managing Candida infections in the oral cavity by modulating the oral microbiota with probiotic bacteria has been proposed. Objective: The aim was to investigate the antifungal potential of the probiotic bacterium Lactobacillus reuteri (DSM 17938 and ATCC PTA 5289) against six oral Candida species (C. albicans, C. glabrata, C. krusei, C. tropicalis, C. dubliniensis, and C. parapsilosis). Design: The lactobacilli were tested for their ability to co-aggregate with and inhibit the growth of the yeasts assessed by spectrophotometry and the agar overlay inhibition assay. Additionally, the pH was evaluated with microsensors, and the production of hydrogen peroxide (H2O2) by the lactobacilli was verified. Results: Both L. reuteri strains showed co-aggregation abilities with the yeasts. The lactobacilli almost completely inhibited the growth of C. albicans and C. parapsilosis, but did not affect C. krusei. Statistically significant differences in co-aggregation and growth inhibition capacities between the two L. reuteri strains were observed (p<0.001). The pH measurements suggested that C. krusei can resist the acids produced by the lactobacilli. Conclusions:L. reuteri exhibited antifungal properties against five of the six most common oral Candida species. Further, the results reconfirms that the probiotic capacity of L. reuteri is strain specific.

Lactobacillus reuteri supplements do not affect salivary IgA or cytokine levels in healthy subjects: A randomized, double-blind, placebo-controlled, cross-over trial.

OBJECTIVES: To evaluate the effect of daily ingestion of probiotic lactobacilli on the levels of secretory IgA (sIgA) and selected cytokines in whole saliva of healthy young adults. MATERIALS AND METHODS: The study group consisted of 47 healthy adults (18-32 years) who volunteered for a randomized, double-blind, placebo-controlled, cross-over trial after informed consent. During intervention, the subjects ingested two lozenges per day containing two strains of the probiotic bacterium Lactobacillus reuteri (DSM 17938 and ATCC PTA 5289) or placebo lozenges. The intervention and wash-out periods were 3 weeks. Saliva samples were collected at baseline, immediately after each intervention period and 3 weeks post-intervention. ELISA was used to measure sIgA and luminex technology was used to measure the interleukins (IL)-1ß, IL-6, IL-8 and IL-10. For statistical analyses a mixed ANOVA model was employed to calculate changes in the salivary outcome variables. RESULTS: Forty-one subjects completed the study and reported a good compliance. No significant differences in the concentrations of salivary sIgA or cytokines were recorded between the L. reuteri and placebo interventions or between baseline and 3 weeks post-intervention levels. No side- or adverse effects were reported. CONCLUSIONS: Supplementation with two strains of the probiotic L. reuteri did not affect sIgA or cytokine levels in whole saliva in healthy young adults. The results thereby indicate that daily oral supplementation with L. reuteri do not seem to modulate the salivary oral immune response in healthy young subjects (ClinicalTrials.gov NCT02017886).

The prognostic value of histopathology on lingual nerve neurosensory recovery after micro-neurosurgery.

OBJECTIVE: Micro-neurosurgical repair is considered in permanent nerve damage but the outcome is unpredictable. We examined if histopathologic parameters of traumatic neuromas have a prognostic value for recovery in relation to lingual nerve micro-neurosurgery. MATERIALS AND METHODS: Retrospective case study on neurosensory recovery after micro-neurosurgery. Outcome variables were as follows: pain perception, two-point discrimination, and sum score of perception, before and 12 months after micro-neurosurgery. Predictive histopathology variables included size, nerve tissue, and inflammation. Statistics are as follows: logistic and correlation analyses (P < 0.05). RESULTS: Sixty-five patients with lingual nerve damage were included in the study. Improved two-point discrimination was associated with small size of resected tissue (P = 0.0275). No normal appearing distal nerve tissue was associated with improved sum score of perception (P = 0.0185), higher final sum score of perception value (P = 0.0475) and final pain perception (P = 0.0324). Foreign body reaction was associated with no final pain perception (P = 0.0492). CONCLUSIONS: Small size, absence of distal nerve tissue, and no foreign body reaction were associated with improvement of the neurosensory functions. CLINICAL RELEVANCE: Histological parameters of the traumatic neuromas in routine preparation appeared to have some prognostic value for neurosensory functions as improvement of the neurosensory functions was associated with small size of resected tissue, no distal normal appearing nerve tissue, and no foreign body reaction.

[Infections of the oral mucosa]. / Infektioner i mundslimhinden.

The most common infections of the oral mucosa are those caused by Candida albicans and herpes simplex virus (HSV). Candidosis occurs as pseudomembraneous, erythematous and hyperplastic types with varying symptoms from no to a burning sensation. Treatment most importantly includes elimination of any predisposing factors such as smoking, sub-optimal denture hygiene and hyposalivation. A primary HSV infection results in a life-long latent infection recurring in some infected persons either intraorally or on the lip. If treatment is indicated, topical or systemic aciclovir and related drugs can be used.

ORAL ADVERSE DRUG REACTIONS TO CARDIOVASCULAR DRUGS.

A great many cardiovascular drugs (CVDs) have the potential to induce adverse reactions in the mouth. The prevalence of such reactions is not known, however, since many are asymptomatic and therefore are believed to go unreported. As more drugs are marketed and the population includes an increasing number of elderly, the number of drug prescriptions is also expected to increase. Accordingly, it can be predicted that the occurrence of adverse drug reactions (ADRs), including the oral ones (ODRs), will continue to increase. ODRs affect the oral mucous membrane, saliva production, and taste. The pathogenesis of these reactions, especially the mucosal ones, is largely unknown and appears to involve complex interactions among the drug in question, other medications, the patient's underlying disease, genetics, and life-style factors. Along this line, there is a growing interest in the association between pharmacogenetic polymorphism and ADRs. Research focusing on polymorphism of the cytochrome P450 system (CYPs) has become increasingly important and has highlighted the intra- and inter-individual responses to drug exposure. This system has recently been suggested to be an underlying candidate regarding the pathogenesis of ADRs in the oral mucous membrane. This review focuses on those CVDs reported to induce ODRs. In addition, it will provide data on specific drugs or drug classes, and outline and discuss recent research on possible mechanisms linking ADRs to drug metabolism patterns. Abbreviations used will be as follows: ACEI, ACE inhibitor; ADR, adverse drug reaction; ANA, antinuclear antigen; ARB, angiotensin II receptor blocker; BAB, beta-adrenergic blocker; CCB, calcium-channel blocker; CDR, cutaneous drug reaction; CVD, cardiovascular drug; CYP, cytochrome P450 enzyme; EM, erythema multiforme; FDE, fixed drug eruption; I, inhibitor of CYP isoform activity; HMG-CoA, hydroxymethyl-glutaryl coenzyme A; NAT, N-acetyltransferase; ODR, oral drug reaction; RDM, reactive drug metabolite; S, substrate for CYP isoform; SJS, Stevens-Johnson syndrome; SLE, systemic lupus erythematosus; and TEN, toxic epidermal necrolysis.