Effects of the combined action of a desensitizing gel and toothpaste on dentin hypersensitivity due to dental bleaching

Objectives: The present study is aimed at evaluating the effectiveness of a fluoride- and potassium nitrate-containing gel and toothpaste in reducing dentinal hypersensitivity due to dental bleaching. Materials and methods: Specific inclusion and exclusion criteria were used to recruit patients for the study. They were randomly allocated to a test or a placebo control group. Patients underwent a treatment of home dental bleaching with 10% carbamide peroxide. Dental shades were evaluated in a standardized environment and dentinal hypersensitivity was valuated by means of evaporation stimuli. A nominal scale was used to score the painful reaction. The patients were recalled 8, 15 and 28 days after the baseline for both shade and sensitivity assessment. Statistical analysis was performed using the Student’s T-test. Results: The patients recall rate was 96.9%. The statistical analysis demonstrated a significant reduction of the painful symptoms in the experimental group (p=0.031) while no statistically significant differences were evidenced in the control group at any follow-up recall (p>0.05). Discussion: The tested agents proved to be safe and effective in the short term. Neither pigmentations nor interferences with the bleaching action of peroxides due to the desensitizing agents were observed. The compliance of the patients to the proposed protocol as well as the motivation to maintain good oral hygiene were paramount in the achievement of the reported results. Conclusions: The use of a desensitizing gel and toothpaste containing fluoride and potassium nitrate was effective in reducing dentinal hypersensitivity due to dental bleaching and did not interfere with the bleaching action of peroxides. Clinical significance: Desensitizing gels and toothpastes containing fluoride and potassium nitrate can be considered safe and effective in the control of tooth sensitivity after dental bleaching

Long term evaluation of mental fatigue by Maastricht Questionnaire in patients with OSAS treated with CPAP

Background. Patients with obstructive sleep apnoea syndrome (OSAS) suffer from disrupted sleep. Impaired nightly sleep leads to increase physical and mental fatigue. The effect of long term continuous positive airway pressure (CPAP) on mental fatigue in OSAS patients, assessed by Maastricht Questionnaire (MQ), has not been investigated yet. Methods. In order to evaluate the role of CPAP in improving mental fatigue of patients with OSAS, we studied 35 patients (26 males, age <65 years at the time of the diagnosis) affected by OSAS, established by polysomnography (PSG). Patients were divided into two groups; 19 subjects (15 males), who refused CPAP therapy, and 16 patients (11 males) well matched for sex, age, body mass index (BMI), neck circumference, duration of follow up, and severity of disease, who had been treated with CPAP for at least two years. Results. All patients had severe OSAS with Respiratory Disturbance Index (RDI), of 48±20.9 (range 22-90) and 61.48±18.6 (range 34-101) respectively, for group one (untreated patients) and group two (CPAP treatment). In addition, all patients had severe impairment of mental fatigue and of daytime sleepiness, demonstrated by high values of MQ score (32.17±15.33 and 37.36±12.4, respectively) and Epworth Sleepiness Scale (ESS) (14.21±4.77 and 15.06±6.07 respectively). There was no statistical significant difference in the group one at baseline and after follow- up, in terms of BMI, MQ score, ESS, and RDI. In the CPAP group (group two), the patients reported a significant improvement of the quality of their mental health (MQ 37.36±12.4 vs. 16.41±9.02; p<0.0001) and sleepiness (ESS 15.06±6.07 vs. 4.13±3.93; p<0.0001) with a stable BMI. There was significant correlation between the severity of sleep apnoea, expressed as RDI, and MQ at admission compared to at the end of follow-up (r=0.4, p<0.05). Conclusions. This study demonstrates an evident deterioration of mental fatigue in patients with OSAS, directly correlated to the severity of nocturnal disorder breathing; however supports the hypothesis that long term CPAP therapy significantly improves sleepiness and mental fatigue

A case of cryptogenic organizing pneumonia occurring in Crohn's disease.

A 29 year-old-man with Crohn's disease, who developed diffuse pulmonary infiltrates and hypoxemia two months following oral administration of mesalazine, was examined. Clinical findings and computed tomography were suggestive of, and lung histology was diagnostic of, bronchiolitis obliterans organizing pneumonia, also known as cryptogenic organizing pneumonia. Although the data did not allow for definitive conclusions, they did suggest that the pulmonary disease was an extraintestinal manifestation of Crohn's disease, rather than an adverse reaction to mesalazine. In fact, the patient showed clinical, radiological and functional improvements, despite the treatment with mesalazine and the withdrawal of steroid therapy

Increased IL-6 and IL-4 in exhaled breath condensate of patients with nasal polyposis

Background and Aim. Nasal polyposis (NP) occurs in about 1-4% of the worldwide population. Increased plasma concentrations of different pro-inflammatory cytokines have been observed in NP, and might be related to the pathogenesis of this syndrome.The present study was designed to investigate IL-6 and IL-4 concentrations in nasal and oral exhaled breath condensate of patients with early and advanced NP, and following polypectomy. Methods. Ten individuals with polyposis in early status, twenty-three patients affected by advanced status of NP and ten healthy controls were enrolled into the study. Exhaled breath condensate was collected by all individuals, according to a previous standardised method. An immunoassay kit was used to measure IL-6 and IL-4 levels. Results. Concentrations of oral and nasal exhaled IL- 6 and IL-4 were significantly higher in patients with early nasal polyposis and advanced nasal polyposis, compared to healthy controls. A statistically significant decrease of nasally but not of orally exhaled IL-6 (p<0.001) and IL-4 (p<0.05) was observed after polypectomy. Conclusions. We consider oral and nasal exhaled condensate of IL-6 and IL-4 as valid inflammatory and oxidative stress marker in patients with nasal polyposis

Cannabidiol Reduces Aβ-Induced Neuroinflammation and Promotes Hippocampal Neurogenesis through PPARγ Involvement

Peroxisome proliferator-activated receptor-γ (PPARγ) has been reported to be involved in the etiology of pathological features of Alzheimer's disease (AD). Cannabidiol (CBD), a Cannabis derivative devoid of psychomimetic effects, has attracted much attention because of its promising neuroprotective properties in rat AD models, even though the mechanism responsible for such actions remains unknown. This study was aimed at exploring whether CBD effects could be subordinate to its activity at PPARγ, which has been recently indicated as its putative binding site. CBD actions on β-amyloid-induced neurotoxicity in rat AD models, either in presence or absence of PPAR antagonists were investigated. Results showed that the blockade of PPARγ was able to significantly blunt CBD effects on reactive gliosis and subsequently on neuronal damage. Moreover, due to its interaction at PPARγ, CBD was observed to stimulate hippocampal neurogenesis. All these findings report the inescapable role of this receptor in mediating CBD actions, here reported

Palmitoylethanolamide exerts neuroprotective effects in mixed neuroglial cultures and organotypic hippocampal slices via peroxisome proliferator-activated receptor-α

<p>Abstract</p> <p>Background</p> <p>In addition to cytotoxic mechanisms directly impacting neurons, β-amyloid (Aβ)-induced glial activation also promotes release of proinflammatory molecules that may self-perpetuate reactive gliosis and damage neighbouring neurons, thus amplifying neuropathological lesions occurring in Alzheimer's disease (AD). Palmitoylethanolamide (PEA) has been studied extensively for its anti-inflammatory, analgesic, antiepileptic and neuroprotective effects. PEA is a lipid messenger isolated from mammalian and vegetable tissues that mimics several endocannabinoid-driven actions, even though it does not bind to cannabinoid receptors. Some of its pharmacological properties are considered to be dependent on the expression of peroxisome proliferator-activated receptors-α (PPARα).</p> <p>Findings</p> <p>In the present study, we evaluated the effect of PEA on astrocyte activation and neuronal loss in models of Aβ neurotoxicity. To this purpose, primary rat mixed neuroglial co-cultures and organotypic hippocampal slices were challenged with Aβ_1-42and treated with PEA in the presence or absence of MK886 or GW9662, which are selective PPARα and PPARγ antagonists, respectively. The results indicate that PEA is able to blunt Aβ-induced astrocyte activation and, subsequently, to improve neuronal survival through selective PPARα activation. The data from organotypic cultures confirm that PEA anti-inflammatory properties implicate PPARα mediation and reveal that the reduction of reactive gliosis subsequently induces a marked rebound neuroprotective effect on neurons.</p> <p>Conclusions</p> <p>In line with our previous observations, the results of this study show that PEA treatment results in decreased numbers of infiltrating astrocytes during Aβ challenge, resulting in significant neuroprotection. PEA could thus represent a promising pharmacological tool because it is able to reduce Aβ-evoked neuroinflammation and attenuate its neurodegenerative consequences.</p

SCD1 Inhibition Causes Cancer Cell Death by Depleting Mono-Unsaturated Fatty Acids

Increased metabolism is a requirement for tumor cell proliferation. To understand the dependence of tumor cells on fatty acid metabolism, we evaluated various nodes of the fatty acid synthesis pathway. Using RNAi we have demonstrated that depletion of fatty-acid synthesis pathway enzymes SCD1, FASN, or ACC1 in HCT116 colon cancer cells results in cytotoxicity that is reversible by addition of exogenous fatty acids. This conditional phenotype is most pronounced when SCD1 is depleted. We used this fatty-acid rescue strategy to characterize several small-molecule inhibitors of fatty acid synthesis, including identification of TOFA as a potent SCD1 inhibitor, representing a previously undescribed activity for this compound. Reference FASN and ACC inhibitors show cytotoxicity that is less pronounced than that of TOFA, and fatty-acid rescue profiles consistent with their proposed enzyme targets. Two reference SCD1 inhibitors show low-nanomolar cytotoxicity that is offset by at least two orders of magnitude by exogenous oleate. One of these inhibitors slows growth of HCT116 xenograft tumors. Our data outline an effective strategy for interrogation of on-mechanism potency and pathway-node-specificity of fatty acid synthesis inhibitors, establish an unambiguous link between fatty acid synthesis and cancer cell survival, and point toward SCD1 as a key target in this pathway

Heat stress causes spatially-distinct membrane re-modelling in K562 leukemia cells

Cellular membranes respond rapidly to various environmental perturbations. Previously we showed that modulations in membrane fluidity achieved by heat stress (HS) resulted in pronounced membrane organization alterations which could be intimately linked to the expression and cellular distribution of heat shock proteins. Here we examine heat-induced membrane changes using several visualisation methods. With Laurdan two-photon microscopy we demonstrate that, in contrast to the enhanced formation of ordered domains in surface membranes, the molecular disorder is significantly elevated within the internal membranes of cells preexposed to mild HS. These results were compared with those obtained by anisotropy, fluorescence lifetime and electron paramagnetic resonance measurements. All probes detected membrane changes upon HS. However, the structurally different probes revealed substantially distinct alterations in membrane heterogeneity. These data call attention to the careful interpretation of results obtained with only a single label. Subtle changes in membrane microstructure in the decision-making of thermal cell killing could have potential application in cancer therapy

NADPH oxidase elevations in pyramidal neurons drive psychosocial stress-induced neuropathology

Oxidative stress is thought to be involved in the development of behavioral and histopathological alterations in animal models of psychosis. Here we investigate the causal contribution of reactive oxygen species generation by the phagocyte NADPH oxidase NOX2 to neuropathological alterations in a rat model of chronic psychosocial stress. In rats exposed to social isolation, the earliest neuropathological alterations were signs of oxidative stress and appearance of NOX2. Alterations in behavior, increase in glutamate levels and loss of parvalbumin were detectable after 4 weeks of social isolation. The expression of the NOX2 subunit p47phox was markedly increased in pyramidal neurons of isolated rats, but below detection threshold in GABAergic neurons, astrocytes and microglia. Rats with a loss of function mutation in the NOX2 subunit p47phox were protected from behavioral and neuropathological alterations induced by social isolation. To test reversibility, we applied the antioxidant/NOX inhibitor apocynin after initiation of social isolation for a time period of 3 weeks. Apocynin reversed behavioral alterations fully when applied after 4 weeks of social isolation, but only partially after 7 weeks. Our results demonstrate that social isolation induces rapid elevations of the NOX2 complex in the brain. Expression of the enzyme complex was strongest in pyramidal neurons and a loss of function mutation prevented neuropathology induced by social isolation. Finally, at least at early stages, pharmacological targeting of NOX2 activity might reverse behavioral alterations

HPV16 E7-Dependent Transformation Activates NHE1 through a PKA-RhoA-Iinduced Inhibition of p38alpha

Background: Neoplastic transformation originates from a large number of different genetic alterations. Despite this genetic variability, a common phenotype to transformed cells is cellular alkalinization. We have previously shown in human keratinocytes and a cell line in which transformation can be turned on and followed by the inducible expression of the E7 oncogene of human papillomavirus type 16 (HPV16), that intracellular alkalinization is an early and essential physiological event driven by the up-regulation of the Na/H-+(+) exchanger isoform 1 (NHE1) and is necessary for the development of other transformed phenotypes and the in vivo tumor formation in nude mice.Methodology: Here, we utilize these model systems to elucidate the dynamic sequence of alterations of the upstream signal transduction systems leading to the transformation-dependent activation of NHE1.Principal Findings: We observe that a down-regulation of p38 MAPK activity is a fundamental step in the ability of the oncogene to transform the cell. Further, using pharmacological agents and transient transfections with dominant interfering, constitutively active, phosphorylation negative mutants and siRNA strategy to modify specific upstream signal transduction components that link HPV16 E7 oncogenic signals to up-regulation of the NHE1, we demonstrate that the stimulation of NHE1 activity is driven by an early rise in cellular cAMP resulting in the down-stream inhibition of p38 MAPK via the PKA-dependent phosphorylation of the small G-protein, RhoA, and its subsequent inhibition.Conclusions: All together these data significantly improve our knowledge concerning the basic cellular alterations involved in oncogene-driven neoplastic transformation