Effects of various forms of calcium added to chewing gum on initial enamel carious lesions in situ

The purpose of this randomized, cross-over in situ study was to determine the effects of 4 chewing gums on artificial caries-like subsurface lesions. Two chewing gums (1 with zinc citrate and 1 without) contained dicalcium phosphate (3.9%), calcium gluconate (1.8%) and calcium lactate (0.45%), 1 chewing gum contained casein phosphopeptide-amorphous calcium phosphate nanocomplexes (0.7%), and another one contained no calcium. Fifteen subjects without current caries activity (7 male, 8 female; mean age: 27.5 +/- 2.5 years) wore removable buccal appliances in the lower jaw with 4 bovine enamel slabs with subsurface lesions. The appliances were inserted immediately before gum chewing for 20 min and then retained for an additional 20 min. This was performed 4 times per day. Every subject chewed 4 different chewing gums over 4 periods of 14 days each. During a fifth period (control) the subjects only wore the appliances without chewing gum. At completion of each period the enamel slabs were embedded, sectioned and subjected to transversal microradiography. With regard to change of mineral loss and of lesion depth no significant differences could be found between chewing gums containing calcium and calcium-free chewing gums. Moreover, the chewing gum groups and the control group did not differ significantly if adjustments were made for baseline values (p > 0.05; ANCOVA). Under the conditions of the present study it may be concluded that the use of chewing gum offers no additional remineralizing benefit to buccal tooth surfaces, even if the chewing gum contains calcium compounds.

Calcium waves driven by "sensitization" wave-fronts

OBJECTIVE: Cellular Ca(2+) waves are understood as reaction-diffusion systems sustained by Ca(2+)-induced Ca(2+) release (CICR) from Ca(2+) stores. Given the recently discovered sensitization of Ca(2+) release channels (ryanodine receptors; RyRs) of the sarcoplasmic reticulum (SR) by luminal SR Ca(2+), waves could also be driven by RyR sensitization, mediated by SR overloading via Ca(2+) pump (SERCA), acting in tandem with CICR. METHODS: Confocal imaging of the Ca(2+) indicator fluo-3 was combined with UV-flash photolysis of caged compounds and the whole-cell configuration of the patch clamp technique to carry out these experiments in isolated guinea pig ventricular cardiomyocytes. RESULTS: Upon sudden slowing of the SERCA in cardiomyocytes with a photoreleased inhibitor, waves indeed decelerated immediately. No secondary changes of Ca(2+) signaling or SR Ca(2+) content due to SERCA inhibition were observed in the short time-frame of these experiments. CONCLUSIONS: Our findings are consistent with Ca(2+) loading resulting in a zone of RyR 'sensitization' traveling within the SR, but inconsistent with CICR as the predominant mechanism driving the Ca(2+) waves. This alternative mode of RyR activation is essential to fully conceptualize cardiac arrhythmias triggered by spontaneous Ca(2+) release.

Comparison of calcium analysis, longitudinal microradiography and profilometry for the quantitative assessment of erosion in dentine

Erosion of dentine causes mineral dissolution, while the organic compounds remain at the surface. Therefore, a determination of tissue loss is complicated. Established quantitative methods for the evaluation of enamel have also been used for dentine, but the suitability of these techniques in this field has not been systematically determined. Therefore, this study aimed to compare longitudinal microradiography (LMR), contacting (cPM) and non-contacting profilometry (ncPM), and analysis of dissolved calcium (Ca analysis) in the erosion solution. Results are discussed in the light of the histology of dentine erosion. Erosion was performed with 0.05 M citric acid (pH 2.5) for 30, 60, 90 or 120 min, and erosive loss was determined by each method. LMR, cPM and ncPM were performed before and after collagenase digestion of the demineralised organic surface layer, with an emphasis on moisture control. Scanning electron microscopy was performed on randomly selected specimens. All measurements were converted into micrometres. Profilometry was not suitable to adequately quantify mineral loss prior to collagenase digestion. After 120 min of erosion, values of 5.4 +/- 1.9 microm (ncPM) and 27.8 +/- 4.6 microm (cPM) were determined. Ca analysis revealed a mineral loss of 55.4 +/- 11.5 microm. The values for profilometry after matrix digestion were 43.0 +/- 5.5 microm (ncPM) and 46.9 +/- 6.2 (cPM). Relative and proportional biases were detected for all method comparisons. The mineral loss values were below the detection limit for LMR. The study revealed gross differences between methods, particularly when demineralised organic surface tissue was present. These results indicate that the choice of method is critical and depends on the parameter under study.

Role of calcium, glutamate and NMDA in major depression and therapeutic application

Major depression is a common, recurrent mental illness that affects millions of people worldwide. Recently, a unique fast neuroprotective and antidepressant treatment effect has been observed by ketamine, which acts via the glutamatergic system. Hence, a steady accumulation of evidence supporting a role for the excitatory amino acid neurotransmitter (EAA) glutamate in the treatment of depression has been observed in the last years. Emerging evidence indicates that N-methyl-D-aspartate (NMDA), group 1 metabotropic glutamate receptor antagonists and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) agonists have antidepressant properties. Indeed, treatment with NMDA receptor antagonists has shown the ability to sprout new synaptic connections and reverse stress-induced neuronal changes. Based on glutamatergic signaling, a number of therapeutic drugs might gain interest in the future. Several compounds such as ketamine, memantine, amantadine, tianeptine, pioglitazone, riluzole, lamotrigine, AZD6765, magnesium, zinc, guanosine, adenosine aniracetam, traxoprodil (CP-101,606), MK-0657, GLYX-13, NRX-1047, Ro25-6981, LY392098, LY341495, D-cycloserine, D-serine, dextromethorphan, sarcosine, scopolamine, pomaglumetad methionil, LY2140023, LY404039, MGS0039, MPEP, 1-aminocyclopropanecarboxylic acid, all of which target this system, have already been brought up, some of them recently. Drugs targeting the glutamatergic system might open up a promising new territory for the development of drugs to meet the needs of patients with major depression.

Optimization of TRPV6 Calcium Channel Inhibitors Using a 3D Ligand-Based Virtual Screening Method

Herein, we report the discovery of the first potent and selective inhibitor of TRPV6, a calcium channel overexpressed in breast and prostate cancer, and its use to test the effect of blocking TRPV6-mediated Ca2+-influx on cell growth. The inhibitor was discovered through a computational method, xLOS, a 3D-shape and pharmacophore similarity algorithm, a type of ligand-based virtual screening (LBVS) method described briefly here. Starting with a single weakly active seed molecule, two successive rounds of LBVS followed by optimization by chemical synthesis led to a selective molecule with 0.3 μM inhibition of TRPV6. The ability of xLOS to identify different scaffolds early in LBVS was essential to success. The xLOS method may be generally useful to develop tool compounds for poorly characterized targets.

Historic records of organic compounds from a high Alpine glacier: influences of biomass burning, anthropogenic emissions, and dust transport

Historic records of α-dicarbonyls (glyoxal, methylglyoxal), carboxylic acids (C6–C12 dicarboxylic acids, pinic acid, p-hydroxybenzoic acid, phthalic acid, 4-methylphthalic acid), and ions (oxalate, formate, calcium) were determined with annual resolution in an ice core from Grenzgletscher in the southern Swiss Alps, covering the time period from 1942 to 1993. Chemical analysis of the organic compounds was conducted using ultra-high-performance liquid chromatography (UHPLC) coupled to electrospray ionization high-resolution mass spectrometry (ESI-HRMS) for dicarbonyls and long-chain carboxylic acids and ion chromatography for short-chain carboxylates. Long-term records of the carboxylic acids and dicarbonyls, as well as their source apportionment, are reported for western Europe. This is the first study comprising long-term trends of dicarbonyls and long-chain dicarboxylic acids (C6–C12) in Alpine precipitation. Source assignment of the organic species present in the ice core was performed using principal component analysis. Our results suggest biomass burning, anthropogenic emissions, and transport of mineral dust to be the main parameters influencing the concentration of organic compounds. Ice core records of several highly correlated compounds (e.g., p-hydroxybenzoic acid, pinic acid, pimelic, and suberic acids) can be related to the forest fire history in southern Switzerland. P-hydroxybenzoic acid was found to be the best organic fire tracer in the study area, revealing the highest correlation with the burned area from fires. Historical records of methylglyoxal, phthalic acid, and dicarboxylic acids adipic acid, sebacic acid, and dodecanedioic acid are comparable with that of anthropogenic emissions of volatile organic compounds (VOCs). The small organic acids, oxalic acid and formic acid, are both highly correlated with calcium, suggesting their records to be affected by changing mineral dust transport to the drilling site.