Evaluation of the antibacterial activity of cinnamon essential oil and its individual compounds on Aggregatibacter actinomycetemcomitans isolated from black extrinsic tooth stain: an in vitro study.

AIM: Black extrinsic tooth stain (BETS) is a health challenge that commonly affects children. Aggregatibacter actinomycetemcomitans (Aa) presents in higher prevalence within the polymicrobial community of BETS. In this study, the anti-planktonic and anti-sessile activities of cinnamon essential oil (CEO) and its individual compounds against Aa were evaluated. The preventive effect of CEO and its active substances on BETS formation was also studied in vitro. METHODS: Aa was isolated from a preschool child with BETS and was identified based on the morphological characteristics, MALDI-TOF mass spectroscopy and 16S rRNA sequencing. The effect of CEO and its individual compounds on the growth kinetics of planktonic and sessile Aa cells as well as their antibacterial efficacy and their rate of bacterial killing were examined. The preventive effect of CEO and its active substances on the formation of BETS was evaluated using an ex vivo model. The data were analysed using one-way analysis of variance (ANOVA) and the significance level was set at p < 0.05. RESULTS: Out of eight individual compounds of CEO, only eugenol, cinnamaldehyde and α-methyl cinnamaldehyde showed anti-Aa activities. The values of the minimum inhibitory concentrations (MICs) were in the following order: CEO (421.5 mg/ml) > α-methyl cinnamaldehyde (26.37 mg/ml) > cinnamaldehyde (0.209 mg/ml) > eugenol (0.052 mg/ml). CEO, eugenol, cinnamaldehyde and α-methyl cinnamaldehyde, respectively, exhibited two-, four-, four- and eightfold increase of sessile MIC compared to their planktonic MIC. The growth kinetics of both planktonic and sessile Aa in the presence of CEO, eugenol, cinnamaldehyde and α-methyl cinnamaldehyde revealed a complete inhibition at the MICs and 5.3%-37.4% biofilm inhibition at sub-MICs. The time-killing study demonstrated that CEO, eugenol and cinnamaldehyde were capable of reducing the survival rate of both planktonic and sessile Aa cells after 15-20 and 25-30 min, respectively. However, α-methyl cinnamaldehyde showed a superior anti-planktonic to anti-biofilm activity. The daily incorporation of CEO, eugenol and cinnamaldehyde at their MICs for 14 days totally prevented the formation of BETS in the ex vivo model; however, in the case of α-methyl cinnamaldehyde, BETS was visually detectable after 10 days. CONCLUSION: CEO and its individual compounds have marked antibacterial activity against Aa. The effective results against planktonic and sessile Aa within reasonable time indicate that they can be used to prevent BETS.

Evaluation of the antibacterial activity of Enamelast® and Fluor defender® fluoride varnishes against Streptococcus mutans biofilm: an in vitro study in primary teeth.

PURPOSE: The aim of the current work was to compare the antibacterial activity of Enamelast® and Fluor defender® fluoride varnish on biofilm generation by Streptococcus mutans on extracted primary teeth. METHODS: Thirty-six primary molars were collected and sliced into seventy-two test model disks. All specimens were examined, and the cracked or broken ones were discarded. A total number of specimens (n = 54) were divided into two experimental analyses viz; biofilm formation (n = 27) and microscopic examination (n = 27). Specimens of each analysis were tested under different experimental conditions: a negative control group (n = 9), Fluor defender group (n = 9), and Enamelast group (n = 9). Following treatment, biofilms were generated by adherent Streptococcus mutans on the test model disks on three time intervals: 24 h (n = 3), 48 h (n = 3), and 72 h (n = 3) for each analysis. Then, for biofilm formation analysis, the biofilm was detected spectrophotometrically at 620 nm after being stained by crystal violet. For microscopical analysis, the surfaces of the test model disks were visualized by scanning electron microscopy (SEM), and each image was processed and analyzed using ImageJ software. RESULTS: At 48 and 72 h, Enamelast® and Fluor defender®-treated group showed significantly (p < 0.001) slight adhered bacterial cells when compared with the negative control group as revealed by the absorbance and SEM. Compared with the Fluor defender®-treated group, the absorbance of the Enamelast®-treated group showed a significant (p < 0.001) increase by approximately 7- and 16.5-fold at 48 and 72 h, respectively. Similarly, SEM showed that the number of bacterial cells adhered to enamel surfaces in the Fluor defender®-treated group was significantly (p < 0.001) fewer than the Enamelast®-treated group by approximately 36.55% and 20.62% at 48 and 72 h after exposure, respectively. CONCLUSION: We conclude that the anti-biofilm activity of Fluor defender® against Streptococcus mutans was significantly (p < 0.001) greater than Enamelast® fluoride varnish. The use of Fluor defender® is encouraged as a preventive measure in children with the high risk of developing dental caries.

The wake-promoting drug modafinil stimulates specific hypothalamic circuits to promote adaptive stress responses in an animal model of PTSD.

Pharmacotherapeutic intervention during traumatic memory consolidation has been suggested to alleviate or even prevent the development of posttraumatic stress disorder (PTSD). We recently reported that, in a controlled, prospective animal model, depriving rats of sleep following stress exposure prevents the development of a PTSD-like phenotype. Here, we report that administering the wake-promoting drug modafinil to rats in the aftermath of a stressogenic experience has a similar prophylactic effect, as it significantly reduces the prevalence of PTSD-like phenotype. Moreover, we show that the therapeutic value of modafinil appears to stem from its ability to stimulate a specific circuit within the hypothalamus, which ties together the neuropeptide Y, the orexin system and the HPA axis, to promote adaptive stress responses. The study not only confirms the value of sleep prevention and identifies the mechanism of action of a potential prophylactic treatment after traumatic exposure, but also contributes to understanding mechanisms underlying the shift towards adaptive behavioral response.

Hippocampal microinfusion of oxytocin attenuates the behavioural response to stress by means of dynamic interplay with the glucocorticoid-catecholamine responses.

The neurohypophysial hormone oxytocin acts as a central nervous system neurotransmitter/neuromodulator. We evaluated the effects of oxytocin on behavioural responses to stress, as well as associated biophysiological responses, in a controlled, prospective animal model. The long-term effects of exogenous oxytocin microinjected to the hippocampus of male rats were assessed. Animals were exposed to predator scent stress and treated 1 h or 7 days later with oxytocin or vehicle. Behaviours were assessed with the elevated plus-maze and acoustic startle response tests, 7 days after microinjection and freezing behaviour upon exposure to a trauma-related cue on day 8. These data served for classification into behavioural response groups. Trauma cue response, circulating corticosterone and oxytocin, hippocampal expression of glucocorticoid and mineralocorticoid receptors, and oxytocin receptor mRNA levels were assessed. The interplay between oxytocin, corticosterone and norepinephrine was assessed. Microinfusion of oxytocin both immediately after predator scent stress exposure or 7 days later, after exposure to trauma cue significantly reduced the prevalence rates of extreme responders and reduced trauma cue freezing responses. Post-exposure treatment with oxytocin significantly corrected the corticosterone stress response, decreased glucocorticoid receptor expression and increased mineralocorticoid receptor expression in the hippocampus compared to vehicle treatment. High-dose corticosterone administration together with norepinephrine caused release of plasma oxytocin and hippocampal oxytocin receptor. Oxytocin is actively involved in the neurobiological response to predator scent stress processes and thus warrants further study as a potential therapeutic avenue for the treatment of anxiety-related disorders.

An association between stress-induced disruption of the hypothalamic-pituitary-adrenal axis and disordered glucose metabolism in an animal model of post-traumatic stress disorder.

Retrospective clinical reports suggesting that traumatic stress populations display an increased propensity for glucose metabolism disorders were examined in a controlled prospective animal model. Stress-induced behavioural and hypothalamic-pituitary-adrenal (HPA) axis response patterns were correlated to central and peripheral parameters of glucose metabolism and signalling, and to body measurements in Sprague-Dawley rats exposed to predator scent stress. Forty days post-exposure, fasting blood glucose and insulin levels, oral glucose tolerance test, body weight and white adipose tissue mass, systemic corticosterone levels and brain expression of insulin receptor (IR) and insulin-sensitive glucose transporter 4 (GLUT4) protein levels were evaluated. In a second experiment inbred strains with hyper- (Fischer) and hypo- (Lewis) reactive HPA axes were employed to assess the association of metabolic data with behavioural phenomenology versus HPA axis response profile. For data analysis, animals were classified according to their individual behavioural response patterns (assessed at day 7) into extreme, partial and minimal response groups. The exposed Sprague-Dawley rats fulfilling criteria for extreme behavioural response (EBR) (20.55%) also exhibited significant increases in body weight, abdominal circumference and abdominal white adipose tissue mass; a hyperglycaemic oral glucose tolerance test; and fasting hyperglycaemia, hyperinsulinaemia and hypercorticosteronemia, whereas minimal responders (MBR) and control animals displayed no such disturbances. Hippocampal and hypothalamic expression of IR and GLUT4 protein were significantly lower in EBR than in MBR and control rats. The inbred strains showed no metabolic differences at baseline. Exposed Fischer rats displayed hyperglycaemia and hyperinsulinaemia, whereas Lewis rats did not. A significant protracted disorder of glucose metabolism was induced by exposure to a stress paradigm. This metabolic response was associated with the characteristic pattern of HPA axis (corticosterone) response, which underlies the behavioural response to stress.

Reversal of pathologic cardiac parameters after transition from clozapine to olanzapine treatment: a case report.

Antipsychotic medications have been associated with significant cardiovascular adverse effects and instances of sudden cardiac death. Recently, we started to evaluate cardiac parameters in medicated patients with schizophrenia using power spectrum analysis of heart rate variability. We present a case of a patient with long-standing schizophrenia who was treated with clozapine. His electrocardiogram revealed minor abnormalities, including a prolonged QT interval. Power spectrum analysis of heart rate variability demonstrated marked abnormalities in autonomic nervous system activity. Two years later, his treatment was switched to olanzapine. We reevaluated his cardiac parameters. Power spectrum analysis studies revealed that heart rate had significantly improved and that power spectrum cardiovascular parameters had returned to normal. Serial electrocardiograms revealed a minimally and asymptomatically prolonged QT interval. This case demonstrates the importance of screening electrocardiograms, even in healthy young patients. It also emphasizes how minor changes in electrocardiogram can be overlooked on standard electrocardiograms. Power spectrum analysis of heart rate variability is useful in this instance because it magnifies the trace and detects even minor disturbances. Care should be taken in prescribing antipsychotic drugs to patients who are prone to cardiovascular side effects, and alternatives to antipsychotics with prominent anticholinergic profile, in particular, should be sought.

Autonomic dysregulation in panic disorder and in post-traumatic stress disorder: application of power spectrum analysis of heart rate variability at rest and in response to recollection of trauma or panic attacks.

Power spectral analysis (PSA) of heart rate variability (HRV) offers reliable assessment of cardiovascular autonomic responses, providing a 'window' onto the interaction of peripheral sympathetic and parasympathetic tone. Alterations in HRV are associated with various physiological and pathophysiological processes, and may contribute to morbidity and mortality. Previous studies of posttraumatic stress disorder (PTSD) found lower resting HRV in patients compared to controls, suggesting increased sympathetic and decreased parasympathetic tone. This article describes the analysis of HRV at rest and after psychological stress in panic disorder (PD) patients, in an enlarged sample of PTSD patients, and in healthy control subjects. Standardized heart rate (HR) analysis was carried out in 14 PTSD patients, 11 PD patients and 25 matched controls. ECG recordings were made while subjects were resting ('rest 1'), while recalling the trauma implicated in PTSD, or the circumstances of a severe panic attack, as appropriate ('recall'), and again while resting ('rest 2'). Controls were asked to recall a stressful life event during recall. While both patient groups had elevated HR and low frequency (LF) components of HRV at baseline (suggesting increased sympathetic activity), PTSD patients, unlike PD patients and controls, failed to respond to the recall stress with increases in HR and LF. HRV analysis demonstrates significant differences in autonomic regulation of PTSD and PD patients compared to each other and to control subjects. HRV analysis may augment biochemical studies of peripheral measures in these disorders.

Power spectral analysis of heart rate variability in psychiatry.

Power spectrum analysis of heart rate variability (PSA of HRV) is a promising method, which can be used as an index of cardiac autonomic balance. PSA of HRV is a noninvasive technique, based on ECG sampling of RR interval variation, thus providing a dynamic assessment of sympathetic and parasympathetic tone, reflecting the interactions between the two. It has been shown to have potential value in various laboratory and clinical conditions. It is influenced by many factors such as age, sex, position, breathing, smoking, hour of the day and medications. Different methods of data processing by various authors have often elicited conflicting results. Standard values are not yet available to be used or compared in different settings. From the interest it has raised, it may be expected that this method will be in widespread use in clinical practice in the future, providing a useful tool, both for diagnostic and prognostic purposes, as well as serving as a further aid towards monitoring therapeutic interventions. This review highlights techniques of dynamic assessment of HRV and studies of its clinical applications in psychiatry in particular. It raises the potentially important prognostic implications of protracted autonomic dysfunction in psychiatric patient populations, especially for cardiovascular morbidity and mortality.

Analysis of heart rate variability in posttraumatic stress disorder patients in response to a trauma-related reminder.

BACKGROUND: Spectral analysis of heart rate variability has recently been shown to be a reliable noninvasive test for quantitative assessment of cardiovascular autonomic regulatory responses, providing a dynamic map of sympathetic and parasympathetic interaction. In a prior study exploring the state of hyperarousal characterizing the posttraumatic stress disorder (PTSD) syndrome, the authors described standardized heart rate analysis carried out in 9 PTSD patients at rest, which demonstrated clear-cut evidence of a baseline autonomic hyperarousal state. METHODS: To examine the dynamics of this hyperarousal state, standardized heart rate analysis was carried out in 9 PTSD patients compared to a matched control group of 9 healthy volunteers. Twenty-minute recordings of electrocardiogram in response to a trauma-related cue as opposed to a resting state were performed and analyzed. The PTSD patients were asked to recount the presumed triggering traumatic event, and the control subjects recounted a significant stressful negative life event. RESULTS: Our results show that, whereas the control subjects demonstrated significant autonomic responses to the stressogenic stimulus supplied by the recounting of a major stressful experience, the PTSD patients demonstrated almost no autonomic response to the recounting of the triggering stressful event. The PTSD patients demonstrated a degree of autonomic dysregulation at rest which was comparable to that seen in the control subjects' reaction to the stress model. CONCLUSIONS: The lack of response to the stress model applied in the study appears to imply that PTSD patients experience so great a degree of autonomic hyperactivation at rest, that they are unable to marshal a further stress response to the recounting of the triggering trauma, as compared to control subjects.

Lamotrigine in the treatment of resistant bipolar disorder.

Antiepileptic drugs, such as carbamazepine and sodium valproate, are integral to psychopharmacologic therapy over the last decades. Lamotrigine is a new antiepileptic drug that acts on amino acid neurotransmitters/neuromodulators, most prominently, glutamine, which has been reported to have potential mood-stabilizing effects. The reports on this effect are limited and sparse, and systematic investigations have not been published. Here we present two clinical cases representing atypical patient groups in which lamotrigine was successfully used as an add-on therapy for resistant bipolar depression.

Inositol has behavioral effects with adaptation after chronic administration.

Inositol is a simple dietary polyol that serves as a precursor in important second messenger systems. Inositol in pharmacological doses has been reported recently to be therapeutic in depression, panic disorder and obsessive compulsive disorder. We hereby report effects of inositol on the elevated plus maze model of anxiety. These results should allow development of new inositol analogs that could expand psychoactive drug development possibilities via second messenger manipulation.