MSX1 is differentially expressed in the deepest impacted maxillary third molars.

An impacted third molar is one of the most common dental abnormalities. Among the reasons for impaction the most common are: insufficient space, time of eruption, improper position of the tooth bud, and genetic disruptions. To investigate if runt-related transcription factor 2 (RUNX2), bone morphogenetic protein 2 (BMP2), and msh homeobox 1 (MSX1) are differently expressed depending on the position of the molar, we studied 32 patients who had been referred for surgical removal. An orthopantomogram was used to separate them according to Winter's, and Pell & Gregory's, classifications. Bone samples were harvested during the operation for gene expression assay. The Kruskal-Wallis, Dunn's post hoc, and Spearman's correlation, tests were used to assess the significance of differences. No correlations were found in expression of the genes, and no differences between expression in maxillary and mandibular third molars, nor were they expressed differently according to Winter's or Pell and Gregory's classifications or in relation to impaction of the mandibular ramus. However, MSX1 was expressed differently when account was taken of the depth of impaction in maxillary third molars (p = 0.029), but there was no difference in expression of RUNX2, BMP2, and MSX1 for the Pell and Gregory classification of depth of impaction (p > 0.05). We conclude that MSX1 is expressed differently depending on the depth of maxillary impaction phenotypes.

MACVIA-LR (Fighting Chronic Diseases for Active and Healthy Ageing in Languedoc-Roussillon): A Success Story of the European Innovation Partnership on Active and Healthy Ageing.

The Région Languedoc Roussillon is the umbrella organisation for an interconnected and integrated project on active and healthy ageing (AHA). It covers the 3 pillars of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA): (A) Prevention and health promotion, (B) Care and cure, (C) and (D) Active and independent living of elderly people. All sub-activities (poly-pharmacy, falls prevention initiative, prevention of frailty, chronic respiratory diseases, chronic diseases with multimorbidities, chronic infectious diseases, active and independent living and disability) have been included in MACVIA-LR which has a strong political commitment and involves all stakeholders (public, private, patients, policy makers) including CARSAT-LR and the Eurobiomed cluster. It is a Reference Site of the EIP on AHA. The framework of MACVIA-LR has the vision that the prevention and management of chronic diseases is essential for the promotion of AHA and for the reduction of handicap. The main objectives of MACVIA-LR are: (i) to develop innovative solutions for a network of Living labs in order to reduce avoidable hospitalisations and loss of autonomy while improving quality of life, (ii) to disseminate the innovation. The three years of MACVIA-LR activities are reported in this paper.

Efficacy and safety of the probiotic Lactobacillus paracasei LP-33 in allergic rhinitis: a double-blind, randomized, placebo-controlled trial (GA2LEN Study).

BACKGROUND/OBJECTIVES: An imbalance between Th1 and Th2 cells is involved in allergic rhinitis (AR) that may be improved by probiotics. To test the efficacy of the probiotic Lactobacillus paracasei subsp. paracasei LP-33, a double-blind, placebo-controlled, randomized trial was carried out in patients with AR to grass pollen treated with loratadine and presenting altered quality of life. SUBJECTS/METHODS: Subjects with persistent AR, symptomatic during the grass pollen season, and a positive skin test or specific immunoglobulin E to grass pollens were included by general practitioners (GPs). All received loratadine for 5 weeks. The primary end point was the improvement in Rhinitis Quality of Life (RQLQ) global score at the fifth week of LP-33 consumption compared with placebo (in addition to loratadine). Secondary end points included nasal and ocular symptoms (individual and total symptom scores), visual analogue scale and time of first exacerbation of the symptoms when loratadine was stopped. RESULTS: A total of 425 subjects were included. Using intent-to-treat analysis, the RQLQ global score decreased significantly more in the LP-33 group than in the placebo group (P=0.0255, difference=-0.286 (95% confidence interval (CI): -0.536; -0.035)). No significant differences were noted for the change of the rhinitis total symptom score 5 global score between groups (P=0.1288, difference=-0.452 (95% CI: -1.036; 0.132)). Significant differences in ocular symptoms (RQLQ) were observed between groups (P=0.0029, difference=-0.4087 (95% CI: -0.6768; -0.1407)). CONCLUSIONS: This study performed by GPs shows that LP-33 improves the quality of life of subjects with persistent AR who are currently being treated with an oral H1-antihistamine. Whereas nasal symptoms had not changed, ocular symptoms had consistently improved.

Indoor coal combustion emissions, GSTM1 and GSTT1 genotypes, and lung cancer risk: a case-control study in Xuan Wei, China.

The lung cancer mortality rate in Xuan Wei County, China is among the highest in the country and has been associated with exposure to indoor smoky coal emissions that contain high levels of polycyclic aromatic hydrocarbons. This risk may be modified by variation in metabolism genes, including GSTM1, which encodes an enzyme known to detoxify polycyclic aromatic hydrocarbons. To investigate the relationship between GST genotypes and lung cancer risk in Xuan Wei County, we analyzed GSTM1 and GSTT1 genotypes in a population-based case-control study. A total of 122 lung cancer patients and 122 controls, individually matched by age, sex, and home fuel type, were studied. Compared to subjects who used less than 130 tons of smoky coal during their lifetime, heavier users (> or =130 tons) had a 2.4-fold (95% confidence interval, 1.3-4.4) increased risk of lung cancer. The GSTM1-null genotype was associated with a 2.3-fold (95% confidence interval, 1.3-4.2) increased risk of lung cancer. Furthermore, there was some evidence that smoky coal use was more strongly associated with lung cancer risk among GSTM1-null versus GSTM1-positive individuals. In contrast, the GSTT1 genotype was not significantly associated with lung cancer risk. Our data suggest that the GSTM1-null genotype may enhance susceptibility to air pollution from indoor coal combustion emissions.

Influence of GSTM1 and NAT2 genotypes on the relationship between personal exposure to PAH and biomarkers of internal dose.

This study examined the interaction of glutathione S-transferase (GSTM1) and N acetyltransferase (NAT2) genotypes and personal exposure to carcinogenic polycyclic aromatic hydrocarbons (PAH) with biomarkers of exposure in a cohort of 51 non-smoking women from Bohemia, CZ. The biomarkers included urinary PAH metabolities and white blood cell DNA adducts. Personal PAH exposure was significantly correlated with urinary PAH metabolites for all individuals (r 0.36, p 0.01, n 46). After stratifying by genetic polymorphism the correlation between personal PAH exposure and urinary PAH metabolites increased for individuals with NAT2 slow acetylators (r 0.58, p 0.001, n 29) and the combination of GSTM1 null and NAT2 slow acetylators (r 0.60, p 0.01, n 16). DNA adduct levels were not significantly correlated with personal PAH exposure (r 0.16, p 0.32, n 51), unless restricted to individuals with the GSTM1 gene (r 0.59, p 0.005, n 21). Personal exposure data were essential for elucidating the possible effect of genotypes on the relationship between PAH exposure and these two classes of internal biomarkers. \[This abstract does not necessarily reflect EPA policy.].

Sphingolipid-gated Ca2+ release from intracellular stores of endothelial cells is mediated by a novel Ca(2+)-permeable channel.

Sphingolipid-gated Ca2+ signaling is mediated through Ca(2+)-permeable channels. In this report, we characterize the properties of the channel in a human endothelial cell line (EA.hy926). Ca2+ release from intracellular stores is not antagonized by nifedipine, omega conotoxin G-VIa, or heparin. To further characterize the molecular properties of the channel, we developed a novel assay to directly measure efflux of Ca2+ from intracellular stores of permeabilized Xenopus oocytes. Following size fractionation by sucrose gradient, poly(A)+ RNA from EA.hy926 cells is microinjected into oocytes of Xenopus laevis. We find that the mRNA encoding Ca2+ release activity is approximately 1.5-2.0 kilobases in length. The sphingolipid-gated Ca(2+)-permeable channel is thus likely to be a novel Ca(2+)-permeable channel distinct from other characterized intracellular Ca2+ channels such as the ryanodyne receptor and the inositol 1,4,5-trisphosphate receptor. The method described here provides a new approach to further characterizing this channel and other intracellular Ca2+ channels.

Two inositol 1,4,5-trisphosphate binding sites in rat basophilic leukemia cells: relationship between receptor occupancy and calcium release.

Quantal calcium release is a novel paradigm for second messenger signal transduction which provides spatial and temporal control of calcium release from intracellular stores by inositol 1,4,5-trisphosphate (InsP3). We have proposed a mechanism to account for this phenomenon [Kindman, L. A., & Meyer, T. (1993) Biochemistry 32, 1270-1277], which hypothesized the existence of five channels, each with a different affinity for InsP3. As a direct test of this hypothesis, InsP3 binding to microsomes from RBL cells was examined under conditions similar to those used for calcium release. Scatchard analyses performed under a variety of conditions indicates the presence of high affinity (KD = 0.9 +/- 0.3 nM) and low affinity (KD = 47 +/- 5 nM) InsP3 binding sites. The low affinity sites are more prevalent, constituting 82 +/- 5% of the total. Both sites are identified in the presence and absence of MgATP. Moreover, both sites are selective for InsP3 over InsP4, through high concentrations of InsP4 displace InsP3 from each site (with inhibition constants of 16 and 267 nM InsP4, respectively). The relative abundance of the two InsP3 binding sites is Ca2+ dependent. An increase in Ca2+ from 0.1 to 0.5 microM results in the apparent conversion of a portion of the low affinity sites into high affinity sites into high affinity sites. Ca2+ (0.5 microM) also increased the KD of the low affinity InsP3 binding site. Given the presence of both high and low affinity InsP3 binding sites, two simple mathematical models describing both the kinetics of calcium release and quantal calcium release from RBL cells were developed.(ABSTRACT TRUNCATED AT 250 WORDS)

Studies on beta-adrenoceptors mediating changes in mechanical events and adenosine 3',5'-monophosphate levels. Rat atria.

Increasing concentrations of the functional antagonist carbachol resulted in a shift to the right of the dose-response curves for (--)-isoproterenol-induced positive chronotropic and inotropic responses and a reduction of the maximum degree of response that could be produced relative to that produced by theophylline. Carbachol only reduced the maximum responses to the partial agonist (--)-soterenol. The ED50 value for isoproterenol-induced increases in adenosine 3',5'-monophosphate (cyclic AMP) levels was more than 10-fold larger than those for production of mechanical events and soterenol did not produce a measurable increase in cyclic AMP above baseline values. Soterenol was analyzed as a competitive antagonist of isoproterenol-induced responses and the apparent dissociation constants (KA) for soterenol calculated to be 1.21 X 10(-7) M for receptors mediating positive chronotropic responses, 3.56 X 10(-7) M for receptors mediating positive inotropic responses, and 2.96 X 10(-7) M for receptors mediating increases in cyclic AMP levels. By two additional theoretical models of drug-receptor interactions, the KA values for soterenol were between 1.5 and 4.5 X 10(-7) M. These KA values were essentially the same as the ED50 values for soterenol-induced mechanical effects. By one of the models, the KA for isoproterenol was calculated to be about 2.14 X 10(-8) M, a value close to the ED50 value for isoproterenol-induced increases in cyclic AMP (5.45 X 10(-8) M). These results suggest that the beta-adrenoceptors mediating the three responses in rat atria are of the same type and that differences in concentrations required to produce mechanical vs. cyclic AMP changes results with agonists possessing high efficacy for which there is a receptor reserve.