Ivan Alajbeg

Efficacy and Safety of an Intraoral Electrostimulation Device for Xerostomia Relief: A Multicenter, Randomized Trial

OBJECTIVE To evaluate the efficacy and safety of an intraoral electrostimulation device, consisting of stimulating electrodes, an electronic circuit, and a power source, in treating xerostomia. The device delivers electrostimulation through the oral mucosa to the lingual nerve in order to enhance the salivary reflex. METHODS The device was tested on a sample of patients with xerostomia due to Sjögrens syndrome and other sicca conditions in a 2-stage prospective, randomized, multicenter trial. Stage I was a double-blind, crossover stage designed to compare the effects of the electrically active device with the sham device, each used for 1 month, and stage II was a 3-month open-label stage designed to assess the long-term effects of the active device. Improvement in xerostomia severity from baseline was the primary outcome measure. RESULTS A total of 114 patients were randomized. In stage I, the active device performed better than the sham device for patient-reported xerostomia severity (P<0.002), xerostomia frequency (P<0.05), quality of life impairment (P<0.01), and swallowing difficulty (P<0.02). At the end of stage II, statistically significant improvements were verified for patient-reported xerostomia severity (P<0.0001), xerostomia frequency (P<0.0001), oral discomfort (P<0.001), speech difficulty (P<0.02), sleeping difficulty (P<0.001), and resting salivary flow rate (P<0.01). CONCLUSION Our findings indicate that daily use of the device alleviated oral dryness, discomfort, and some complications of xerostomia, such as speech and sleeping difficulties, and increased salivary output. The results show a cumulative positive effect of the device over the period of the study, from baseline to the end of the trial.

Intraoral electrostimulator for xerostomia relief: a long-term, multicenter, open-label, uncontrolled, clinical trial

OBJECTIVE A previous sham-controlled multinational study demonstrated the short-term efficacy and safety for xerostomia treatment of an intraoral device that delivers electrostimulation to the lingual nerve. The objective of this study was to test the hypothesis that those beneficial effects would be sustained over an 11-month period. STUDY DESIGN The device was tested on a mixed sample of 94 patients with xerostomia in an open-label, uncontrolled, prospective multicenter trial. Statutory outcome assessments were done at 5th, 8th, and 11th months and analyzed by multiple comparisons. RESULTS Improvements achieved at month 5 from baseline were sustained throughout the follow-up period for the primary outcome, xerostomia severity, and the secondary outcomes resting whole salivary flow rate, xerostomia frequency, oral discomfort, and difficulties in speech, swallowing, and sleeping. No significant side effects were detected. CONCLUSIONS The beneficial effects of a removable intraoral electrostimulating device were sustained for an 11-month period.

Is Effect of Low-Level Laser Therapy in Patients with Burning Mouth Syndrome Result of a Placebo?

Forty female participants were included in this study. All had BMS and their average age was 68 years (range 57-85 years). Participants were randomly allocated. In 20 BMS patients, red diode laser with emission of 685nm was applied five times a week during 2 weeks. Another 20 patients with BMS served as a control group and were treated by the same laser, which was switched off. This investigation was single-blinded placcebo-controlled. Burning intensity was recorded by use of visual analogue scale (VAS) every day during 10 days of therapy. LLLT decreased symptom intensity in BMS patients as seen by VAS, but also the symptom intensity decreased in the same manner in the placebo group as wel, where device was switched off.

Development and validation of a liquid chromatography – tandem mass spectrometry method for the quantification of opiorphin in human saliva

Opiorphin, QRFSR-peptide, is a mature product of the PROL1 (proline rich, lacrimal 1) protein that showed beneficial effects in pain management, antidepressant-like actions as well as involvement in colonic motility and erectile physiology. Using opiorphin as a potential biomarker of different pathological states requires the development of robust and sensitive methods. We report a highly sensitive and specific liquid chromatography with tandem mass spectrometric detection (LC-MS/MS) analytical method for the analysis of opiorphin in human saliva. Quantification was based on multiple reaction monitoring using characteristic transitions (m/z 347/120 - as quantifying ion; 347/175 and 347/268 as qualifying ions). The assay was linear in the range of 0-110 ng/ml and the lower limit of quantification reached was 1.0 ng/ml. The intra-day precision and accuracy were between 2.7-5.6% and -2.3 to 3.2%, respectively. The inter-day precision and accuracy were between 10.8-13.7% and -11.0 to 52%, respectively. Mean recovery was 106% and mean matrix effect was 0.97. Opiorphin in TFA treated saliva samples was stable for at least 12h at room temperature and up to 30 days at -20°C. Opiorphin levels in human saliva samples collected from young healthy individuals ranged from 2.8 to 25.9 ng/ml.

Comparison of the composition of some petroleum samples which may be applied for skin and mucous membrane treatment

A particular Croatian petroleum (sample P1) and its three derivatives (samples P2, P3 and P4), potentially applied as healing preparations for skin and mucous membrane treatment, were studied in order to learn their composition and to discriminate them according to two criteria: composition of natural petroleum compounds, and lacking aromatics. Elemental (C, H, N and S) and group composition (by LC, UV/VIS, IR and 1H NMR) were determined and the single component distributions were analyzed (by GC) and identified (by GC-MS). Focussed saturated compounds (n-alkanes, pristane and phytane, drimanes/eudesmanes, steranes and hopanes) were studied in order to emphasize the preservation or destruction of genuine petroleum structures in derivatives. Samples P2 (petroleum-brownish color, petroleum like smell) and P3 (colorless, transparent, slight pine-like odor), were found, now constituting petroleum, to still be composed of the components of their native structure. Compared to sample P1, they were missing light and heavy compounds. While sample P2 contained different compound classes, sample P3 comprised exclusively saturated hydrocarbons, satisfying pharmacopoeias requirement regarding the low aromatics content. Almost a half of sample P3 was composed of cyclic moieties, including terpenoids, possibly responsible for the odor. Samples P1, P2 and P3 were found rather rich in steranes. Sample P4 (colorless, transparent, no smell) was found denaturalized. In spite of high similarity in bulk properties to sample P3, it comprised no detectable amount of n-alkanes, pristane and phytane, or drimanes/eudesmanes, steranes and hopanes (although found rich in oligocycles).

Non-aromatic naphthalane preparation; preliminary clinical study in the treatment of psoriasis vulgaris.

This study aimed to prove the similarity of the composition of non-aromatic Croatian naphthalane (NAN) with brown naphthalane (BN), which is used in the treatment of psoriasis vulgaris. The comparison of the compositions was performed by obtaining GC fingerprints, which were supported by GC-MS data. In spite of remarkable differences in general profiles of the GC chromatograms, lower and medium molecular weight components of NAN were found to be qualitatively the same as the saturated constituents of BN. Quantitatively, lower molecular weight components as well as all n-alkanes were comparatively lower in NAN. NAN, additionally, contained higher molecular weight components, among which there were saturated oligocyclic hydrocarbons (up to pentakishomohopanes), described as responsible for the curing effect of naphthalane. The composition characteristics of NAN including its non-aromatic character made it suitable for a clinical study. In the treatment, the efficacy was determined by means of comparison of Psoriasis Area Severity Indices, PASI, at the beginning and at the end of the therapy. Adult volunteer-patients, nine males and six females, applied NAN over the whole body, except the scalp, at the room temperature for 20 min and this was followed by the selective UVB radiation. After the 3-week therapy, all essential clinical manifestations as erythema, desquamation and infiltration were significantly reduced in 14 patients; in nine cases the improvement was 50-93%, while the state of five patients improved between 25 and 50%. In one case, there was no obvious change. No exacerbation occurred during the therapy period. No adverse effect on hematological or biochemical parameters was noticed.

Study of Croatian non-aromatic naphthalane constituents with skeletons analogous to bioactive compounds.

Non-aromatic Croatian naphthalane (NAN), shown to be efficace in the treatment of psoriasis vulgaris, was studied in order to improve our understanding of its constituents, which may be potentially responsible for its bioactivity. The components steranes and hopanes were analysed. Since NAN is a complex mixture of hydrocarbons, high-resolution GC and GC-MS were applied as the methods of choice in the study. The GC chromatogram of NAN showed a remarkable cluster in which sterane peaks prevail and composed 33+/- 1% of the sample. Identified steranes (by GC-MS) represented almost half of the cluster (48%). They were in the range from norcholestanes up to propyl cholestanes. The amount of alpha-steranes (8.9%) was higher than of beta-steranes (6.4%) and regular steranes (15.3%) dominated in the ratio 17:1 over the rearranged ones (0.9%). Steranes conserved the skeleton of bio-precursors and remained analogues of bioactive compounds, such as of vitamins D and some hormones and corticosteroids. Pentacyclic hydrocarbons hopanes, as derivatives of bacteriohopantetraol which is the physiological equivalent of cholesterol, made 4.7+/-0.2% of NAN.

Time-related Changes in pH, Buffering Capacity and Phosphate and Urea Concentration of Stimulated Saliva

PURPOSE To quantify changes in pH, buffering capacity and hydrogen carbonate, phosphate, protein and urea concentrations of stimulated saliva which occur during a 30-min measurement delay after saliva collection. The correlation between time-related chemical changes and changes of salivary pH and buffering capacity was assessed in order to explain the observed changes in salivary pH and buffering capacity. MATERIALS AND METHODS Stimulated saliva samples were collected from 30 volunteers after inducing salivation by chewing a piece of parafilm. Measurements of salivary variables were made immediately after saliva collection and again 30 min later, during which time the specimens were exposed to the atmosphere in collection cups at room temperature. RESULTS Postponement of measurements resulted in a significant increase in pH and a significant decrease of buffering capacity, phosphate and urea concentration. The results suggest that the time-related pH increase could primarily be attributed to loss of dissolved carbon dioxide from saliva, and confirm the importance of hydrogen carbonate in the neutralisation of hydrogen ions, but they do not support the principle of catalysed phase-buffering for the hydrogen carbonate buffer system in saliva. A decrease in phosphate and urea concentration affects salivary buffering capacity. CONCLUSION This study emphasises the importance of the standardisation of measurement time when measuring salivary pH, buffering capacity, phosphate and urea concentrations following the collection of saliva in order to obtain comparable results. It also provides a partial explanation of the mechanisms underlying the observed changes of pH and buffering capacity over time.

Within-Subject Reliability and between-Subject Variability of Oxidative Stress Markers in Saliva of Healthy Subjects: A Longitudinal Pilot Study

The present study evaluated diurnal variations and day-to-day fluctuations of salivary oxidative stress (OS) markers in healthy adult individuals. Whole unstimulated saliva was collected at 2 time intervals over 3 consecutive days. Glutathione peroxidase (GPX), superoxide dismutase (SOD), total antioxidant capacity (TAC), and uric acid (UA) were analyzed using spectrophotometric methods, while 8-hydroxydeoxyguanosine (8-OHdG) and malondialdehyde (MDA) were determined using immunoassays. No significant differences for salivary OS markers between men and women were observed. For all examined OS markers, no significant day-to-day variations were demonstrated. Significant diurnal variations were found in salivary GPX, TAC and MDA levels. For SOD, TAC, GPX, and UA, good-to-moderate intraindividual coefficients of variations (CVs) were observed in more than 75% of the subjects. For MDA and 8-OHdG, intraindividual CVs > 35% were observed in 60% and 40% of the subjects, respectively. Between-subject variance was wide for all examined OS markers (CV% 30.08%–85.70%). Due to high intraindividual variability in the salivary concentrations of MDA and 8-OHdG, those markers cannot be reliably verified based on single measurements and multiple measurements over several days would provide more reliable information. Salivary SOD, TAC, GPX, and UA proved stable across three days of measurement. Trial Registration. ClinicalTrials.gov NCT03029494. Registered on 2017-01-19.

Mapping Electrical Impedance Spectra of the Healthy Oral Mucosa: a Pilot Study.

OBJECTIVE Electrical impedance is the resistance to the electric current flow through a tissue and depends on the tissues structure and chemical composition. The aim of this study was to map electrical impedance spectra for each region of the healthy oral mucosa. MATERIALS AND METHODS Electrical impedance was measured in 30 participants with healthy oral mucosa. Measurements were performed in 14 points on the right and the left side of the oral cavity, and repeated after 7 and 14 days respectively. RESULTS The lowest values were measured on the tongue dorsum and the highest values were measured on the hard palate. No significant differences were found between the right and the left side. Significantly higher values were found in females on the upper labial mucosa, tongue dorsum and the ventral tongue. Significant difference between smokers and non-smokers on the lower labial mucosa and floor of the mouth was found. Electrical impedance was negatively correlated with salivary flow on the upper labial mucosa, hard palate, tongue dorsum and sublingual mucosa. Higher variability of measurements was found at low frequencies. CONCLUSIONS Electrical impedance mostly depends on the degree of mucosal keratinization. Demographic and clinical factors probably affect its values. Further studies with bigger number of participants are required.