Changes in the Composition of Unstimulated and Stimulated Saliva Due to Chewing Sour Cherry Gum and a Toothbrush Change.

BACKGROUND: Our previous studies demonstrated that sour cherry anthocyanins (AC) reduce the salivary count of Streptococcus mutans and inhibit salivary amylase activity within 30 minutes after chewing AC gum. AC gum and changing toothbrushes after scaling reduced the Gram-negative species in the unstimulated salivary microbiota. The present study examined the effect of AC gums on salivary factors, including changes in microbiome. METHODS: The study was conducted over three weeks with two groups; young adults (18-30) and adults (30-45). Ten participants changed their toothbrushes, while the other 10 participants did not change after the control period. After scaling, all participants received three doses of AC gum daily. The salivary mRNA and protein levels of cytokines, mucins, melatonin, and the microbiota of unstimulated and stimulated saliva were determined by polymerase chain reaction, enzyme-linked immunosorbent assay, and 16S rRNA gene sequencing. RESULTS: Significantly higher levels of tumor necrosis factor α (TNFα), interleukin-1ß (IL-1ß), mucin5B (MUC5B), mucin7 (MUC7), and melatonin were detected in stimulated saliva. Correlation analysis of these factors with the microbiota showed positive correlations with the genera Lachnospiraceae, Eikenella, Saccharibacteria_(TM7), Streptococcus, Prevotella, and Haemophilus. CONCLUSIONS: AC chewing gum has a beneficial effect on the composition of the oral microbiome, and toothbrush replacement leads to changes in the levels of salivary pro-inflammatory cytokines.

Sympathetic activation in heart failure with reduced and mildly reduced ejection fraction: the role of aetiology.

AIM: While sympathetic overactivity in heart failure (HF) with reduced ejection fraction (HFrEF; EF < 40%) is well-documented, it is ill-defined in patients with mildly reduced EF (HFmrEF; EF 40-49%). Furthermore, the significance of ischaemic versus non-ischaemic aetiology in sympathetic activation is also unclear and has yet to be studied in HF. Our goal was to compare muscle sympathetic nerve activity (MSNA) in HFmrEF and HFrEF patients and in healthy subjects, as well as to elucidate the influence of the underlying disease. METHODS AND RESULTS: Twenty-three HFrEF (age 58 ± 10 years), 33 HFmrEF patients (age 61 ± 10 years), including 11 subjects with non-ischaemic cardiomyopathy in each HF groups and 10 healthy controls (age 55 ± 10 years), were studied. MSNA-detected by peroneal microneurography, continuous arterial pressure, and ECG-was recorded. MSNA frequency (burst/min) and incidence (burst/100 cycles) were calculated. Association with the patients' characteristics were assessed, and aetiology-based comparisons were performed. Burst frequency demonstrated a significant stepwise increase in both HFmrEF (41 ± 11 burst/min) and HFrEF (58 ± 17 burst/min, P < 0.001) patients as compared with controls (27 ± 9; P < 0.001 for both HF groups). Similarly, burst incidences were 66 ± 17, 82 ± 15, and 36 ± 10 burst/100 cycles in HFmrEF, HFrEF patients, and in healthy controls, respectively (P < 0.001 for all). Burst frequencies in HF patients showed significant correlation with NT-proBNP levels, and significant inverse correlations with the subjects' mean RR intervals, stroke volumes, pulse pressures, and EF. CONCLUSIONS: Muscle sympathetic nerve activity parameters indicated significant sympathetic activation in both HFmrEF and HFrEF patients as compared with healthy controls with no difference in relation to ischaemic versus non-ischaemic aetiology.

Cardiovagal and sympathetic baroreflex regulation in heart failure / Cardiovagalis és szimpatikus artériás baroreflex szabályozásának vizsgálata szívelégtelenségben.

Összefoglaló. Bevezetés: Az artériás baroreflex-érzékenységi (BRS-) indexek egységnyi nyomásváltozásra adott élettani válaszokat írnak le. Az RR-intervallum gyors válaszait a cardiovagalis BRS-indexekkel, a vasomotorválaszokat az izom szimpatikus idegi aktivitás (MSNA) válaszain alapuló szimpatikus-BRS-indexekkel jellemezzük. Szívelégtelenségben kórosan csökkent értékeik kedvezotlen kimenetelt jeleznek. Betegek és módszerek: A BRS-indexek meghatározhatóságát 52, szívelégtelenségben szenvedo betegben (kor: 59 ± 10 év; EF: 37 ± 11%) és 11, kor szerint illesztett egészséges önkéntesben vizsgáltuk. EKG- és vérnyomásfelvételekbol három cardiovagalis BRS-indexet számítottunk; a növekvo, illetve csökkeno spontán szekvenciák módszerén alapuló up-BRS-t és down-BRS-t, továbbá az alacsony frekvenciatartomány-beli 'cross-spectralis ' indexet, az LF-alfát. Egy perifériás ideg (nervus peroneus) perkután punkciójával detektáltuk az MSNA szimpatikus csúcs incidenciáját (csúcs/100 szívciklus), s ezt korreláltattuk a diastolés nyomás 3 Hgmm sávokba rendezett értékeivel. Így nyertük a szimpatikus BRS jellemzoit, a BRSSY-incidencia-értékeket. Eredmények: Az up- és down-BRS-szekvenciák csak a betegek 19%-ában voltak meghatározhatók, az LF-alfa a 69%-ukban. Azok, akiknél cardiovagalis BRS nem volt meghatározható, szignifikánsan csökkent RR-intervallum-ingadozást és magasabb NT-proBNP-értékeket mutattak. A meghatározható cardiovagalis BRS-indexek nem különítették el a betegeket és a kontrollszemélyeket. A BRSSY-incidencia-érték 58%-ban állt rendelkezésre, s csakúgy, mint maga a "csúcs" incidencia, jól elkülönítette a betegeket és az önkénteseket. A hiányzó baroreflexérték a magas "csúcs" incidenciával állt összefüggésben. Következtetés: A cardiovagalis BRS-értékek csak korlátozottan alkalmasak egészséges önkéntesek és szívelégtelen betegek elkülönítésére, a meghatározhatatlan értékek súlyosabb betegségre utalnak. A BRSSY-incidencia elkülöníti az egészséges és a beteg csoportokat; a hiányzó érték a fokozott szimpatikus aktivitással áll összefüggésben. Orv Hetil. 2021; 162(3): 91-98. INTRODUCTION: Arterial baroreflex sensitivity (BRS) is characterized by the magnitude of physiological responses to arterial pressure changes. Rapid RR interval responses are quantified by cardiovagal BRS parameters, sympathetic responses could be assessed by changes in muscle sympathetic nerve activity (MSNA). Abnormal indices in heart failure are associated with poor outcome. PATIENTS AND METHODS: 52, heart failure patients (age 59 ± 10 years, EF 37 ± 11%), and 11, age-matched healthy volunteers were studied. From ECG and arterial pressure recordings up-BRS and down-BRS values were determined using the method of spontaneous sequences. The low frequency cross-spectral gain, the LF alpha was also determined. Percutaneous puncture of the peroneal nerves allowed determination of MSNA burst incidence (burst/100 cycles), which was correlated to corresponding diastolic pressure bins of 3 mmHg, yielding a sympathetic BRS, the BRSSY-incidence. RESULTS: Up- and down-BRS could be calculated in 19% of the patients, LF alpha was determined in 69%. Those with missing cardiovagal BRS values showed diminished RR interval variation, and higher levels of NT-proBNP. The measurable cardiovagal BRS indices did not separate patients and healthy volunteers. BRSSY-incidence could be determined in 58% of the patients. The sympathetic gain as well as the burst incidence differed significantly between patients and healthy volunteers. Missing BRSSY-incidence was associated with higher burst incidence. CONCLUSION: Cardiovagal BRS indices have limited value in differentiating healthy and heart failure subjects. Incalculable values among patients indicate more severe disease state. BRSSY-incidence does separate healthy and diseased population, the missing BRSSY-incidence values are related to increased sympathetic activity. Orv Hetil. 2021; 162(3): 91-98.

Theory and history of the study of muscle sympathetic nerve activity / Az izom szimpatikus idegaktivitás vizsgálatának elméleti alapjai és története

Heart failure is a rapidly growing epidemic in developed countries. It has been well documented that heart failure is associated with abnormal neurohumoral activation. The autonomic regulation is characterized by decreased parasympathetic and elevated sympathetic activity. While the cardiovagal activity could be easily assessed by various heart rate variability parameters, markers of the sympathetic activity are not readily available. Percutaneous insertion of microelectrodes in a peripheral nerve allows recording of the muscle sympathetic vasomotor nerve activity (MSNA). MSNA shows good correlation with the cardiac sympathetic activity, and also with the levels of circulating catecholamines. Besides determination of the baseline sympathetic activity, rapid sympathetic responses to various stimuli can be also described by changes of MSNA. Elevated MSNA has been documented in several diseases, including hypertension, obesity, myocardial ischemia and renal failure. In heart failure, the elevated MSNA is well correlated to the clinical severity of the patient's conditions, and serves as a prognostic marker of mortality. In our paper, we give a short account of the history of MSNA studies, describe its physiological background and clinical relevance with special regard to heart failure. Orv Hetil. 2020; 161(29): 1190-1199.

Quantification of peripheral whole blood, cell-free plasma and exosome encapsulated mitochondrial DNA copy numbers in patients with atrial fibrillation.

Mitochondrial DNA (mtDNA) copy number changes have been associated with various diseases. Several studies showed that mtDNA content in peripheral blood was associated with oxidative stress and cardiovascular disease. Atrial fibrillation (AF) is one of the severe cardiovascular diseases. We aimed to determine the mtDNA copy numbers in peripheral blood, in cell-free plasma and in exosomes of AF patients and healthy controls. Peripheral blood was drawn from 60 AF patients and 72 healthy controls. DNA was isolated from EDTA blood and plasma. Exosomes were isolated from cell-free plasma and then exosome encapsulated DNA (exoDNA) was extracted. Quantitative-real-time PCR was performed with Human Mitochondrial DNA (mtDNA) Monitoring Primer Set. Statistical analysis of the data was performed. We found statistically significant difference in mtDNA copy numbers in DNA isolated from peripheral whole blood, cell-free plasma and exosome samples of controls' (44.4 ± 18.0, 27.2 ± 30.1, 11.5 ± 8.7), and patients' group (43.4 ± 13.6, 26.2 ± 26.4, 14.5 ± 12.3). However there was no significant difference in mtDNA copy number between the two study groups either in peripheral blood, in cell-free plasma and in exosomes, and even in different sexes and ages. We found the highest copy number of mtDNA in peripheral blood, followed by plasma and exosomes. We did not find differences between patients and controls, neither age nor gender had effect on the mtDNA copy number. According to our results the mtDNA copy numbers did not differ in AF patients.