Investigating the efficacy of a varnish containing gallic acid on remineralization of enamel lesions: an in vitro study.

This study evaluated the efficacy of a formulated remineralizing gallic acid (GA) varnish in treating artificial enamel caries lesions. Fifty-five intact bovine incisors were collected. Enamel blocks (5 × 9 mm) were prepared. A third of each block's surface remained intact. Primary carious lesions were induced on the middle and bottom thirds of the blocks by immersing the samples in a demineralization solution for 6 h. The bottom third of the blocks were further remineralized by randomly applying 0.5%, 2%, or 8% GA varnishes and 2.26% fluoride varnish (V varnish, Vericom, Seoul, Korea), or the varnish base without active ingredients (n = 11 each). The specimens were immersed in a remineralizing solution for 4 h and then subjected to a 2-hour immersion in the demineralizing solution. After six days of pH cycling, the surface microhardness was measured at depths of 30, 75, and 120 µm. The percentage of surface microhardness recovery (SMHR%) was compared among the groups using the Shapiro-Wilk, ANOVA, and Tukey HSD post-hoc tests (α = 0.05). The SMHR% of all experimental groups was higher than the control group at 30 µm (p < 0.05). The 0.5% GA varnish showed the highest SMHR% at all depths; however, the difference with the other experimental groups was significant at a depth of 30 µm (p < 0.05). The SMHR% of the fluoride and the 2% and 8% GA varnishes was comparable at all depths. All treatments potentially remineralize enamel lesions, with 0.5% GA varnish having the greatest effect, particularly on the top surface layer. As such, this newly developed varnish may emerge as a promising alternative to fluoride varnish.

Targeting Protein Kinases and Epigenetic Control as Combinatorial Therapy Options for Advanced Prostate Cancer Treatment.

Prostate cancer (PC), the fifth leading cause of cancer-related mortality worldwide, is known as metastatic bone cancer when it spreads to the bone. Although there is still no effective treatment for advanced/metastatic PC, awareness of the molecular events that contribute to PC progression has opened up opportunities and raised hopes for the development of new treatment strategies. Androgen deprivation and androgen-receptor-targeting therapies are two gold standard treatments for metastatic PC. However, acquired resistance to these treatments is a crucial challenge. Due to the role of protein kinases (PKs) in the growth, proliferation, and metastases of prostatic tumors, combinatorial therapy by PK inhibitors may help pave the way for metastatic PC treatment. Additionally, PC is known to have epigenetic involvement. Thus, understanding epigenetic pathways can help adopt another combinatorial treatment strategy. In this study, we reviewed the PKs that promote PC to advanced stages. We also summarized some PK inhibitors that may be used to treat advanced PC and we discussed the importance of epigenetic control in this cancer. We hope the information presented in this article will contribute to finding an effective treatment for the management of advanced PC.

Effects of HeartWare ventricular assist device on the von Willebrand factor: results of an academic Belgian center.

BACKGROUND: Left Ventricular Assist Device (LVAD) is a promising therapy for patients with advanced heart failure (HF), but bleeding complications remain an important issue. Previous series show that acquired von Willebrand syndrome was present in up to 100 % of first generation LVAD recipients. We report the effects of new generation LVADs on vW factor (vWF) metabolism and activity in our center. METHODS: Fifteen LVAD recipients (HeartWare®, Framingham, MA, USA) were compared to 12 HF patients, matched for age and body mass index. vWF antigen and activity, as well as D-dimers, were measured on hemostasis analyzers. A vWF LVAD-induced alteration was evocated when the [vWF activity]/[vWF antigen] ratio was <0.6. ADAMTS13 and high molecular weight multimers of vWF were also assessed. RESULTS: LVAD recipients had similar levels of endothelial vWF production than the HF subjects (137 ± 14.5 vs. 147 ± 11.7 %; respectively, p = 0.611) but a decreased vWF activity (90 ± 11 vs. 132.6 ± 13 %; respectively, p = 0.017). [vWF activity]/[vWF antigen] ratio was 0.65 ± 0.02 in the LVAD recipients and 0.92 ± 0.06 in the subjects with HF (p = 0.001). ADAMTS13 activity was 80.3 ± 4.7 % in LVAD recipients and 96.2 ± 3.5 % in the HF patients (p = 0.016). LVAD patients disclosed markedly elevated D-dimers (3217.7 ± 735 vs. 680.6 ± 223.2 ng/mL FEU in the HF patients, p = 0.006). The LVAD patients experienced one major hemorrhagic event and one systemic thrombotic event during the median follow-up of 345 days. CONCLUSIONS: LVAD recipients achieved a new hemostatic equilibrium characterized by infrequent major hemorrhagic and thrombotic events, despite a mildly impaired vWF function and a markedly enhanced thrombin formation. TRIAL REGISTRATION: ISRCTN39517567.

At high cardiac output, diesel exhaust exposure increases pulmonary vascular resistance and decreases distensibility of pulmonary resistive vessels.

Air pollution has recently been associated with the development of acute decompensated heart failure, but the underlying biological mechanisms remain unclear. A pulmonary vasoconstrictor effect of air pollution, combined with its systemic effects, may precipitate decompensated heart failure. The aim of the present study was to investigate the effects of acute exposure to diesel exhaust (DE) on pulmonary vascular resistance (PVR) under resting and stress conditions but also to determine whether air pollution may potentiate acquired pulmonary hypertension. Eighteen healthy male volunteers were exposed to ambient air (AA) or dilute DE with a particulate matter of <2.5 µm concentration of 300 µg/m(3) for 2 h in a randomized, crossover study design. The effects of DE on PVR, on the coefficient of distensibilty of pulmonary vessels (α), and on right and left ventricular function were evaluated at rest (n = 18), during dobutamine stress echocardiography (n = 10), and during exercise stress echocardiography performed in hypoxia (n = 8). Serum endothelin-1 and fractional exhaled nitric oxide were also measured. At rest, exposure to DE did not affect PVR. During dobutamine stress, the slope of the mean pulmonary artery pressure-cardiac output relationship increased from 2.8 ± 0.5 mmHg · min · l (-1) in AA to 3.9 ± 0.5 mmHg · min · l (-1) in DE (P < 0.05) and the α coefficient decreased from 0.96 ± 0.15 to 0.64 ± 0.12%/mmHg (P < 0.01). DE did not further enhance the hypoxia-related upper shift of the mean pulmonary artery pressure-cardiac output relationship. Exposure to DE did not affect serum endothelin-1 concentration or fractional exhaled nitric oxide. In conclusion, acute exposure to DE increased pulmonary vasomotor tone by decreasing the distensibility of pulmonary resistive vessels at high cardiac output.

Pro-thrombotic effect of exercise in a polluted environment: a P-selectin- and CD63-related platelet activation effect.

Exposure to diesel exhaust is an important cardiovascular risk factor and may promote atherothrombotic events. Some data suggest that polluted air exposure could affect haemostasis through platelet activation. The aim of the study was to investigate the effects of acute exposure to diesel exhaust on platelet activation and platelet function. We tested the hypothesis in a randomised, crossover study in 25 healthy men exposed to ambient and polluted air; 11 of the subjects also performed exercise during exposure sessions. Platelet activation was evaluated by surface expression of CD62P (P-selectin) and CD63 (dense granule glycoprotein) using flow cytometry of labelled platelets. Platelet function was measured using the PFA-100 platelet function analyser and by Multiplate whole blood impedance platelet aggregometry. Acute diesel exhaust exposure had no effect on platelet activation at rest, but exercise in polluted air increased the collagen-induced expression of CD62P and CD63 (both p< 0.05). The increase in the expression of CD62P and CD63 was related to the total amount of PM2.5 inhaled during the exercise sessions (r=+0.58 and +0.60, respectively, both p< 0.05). Platelet aggregation was not impaired after polluted air exposure at rest or during exercise. In conclusion, in healthy subjects, diesel exhaust exposure induces platelet activation as illustrated by a dose-response increase in the release of CD62P and CD63. This platelet priming effect could be a contributor to the triggering of atherothrombotic events related to air pollution exposure.