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Dysregulated actions of bone-derived phosphaturic hormone fibroblast growth factor 23 (FGF23) result in several inherited diseases, such as X-linked hypophosphatemia (XLH), and contribute substantially to the mortality in kidney failure. Mechanisms governing FGF23 production are poorly defined. We herein found that ablation of the G(q/11)α–like, extralarge Gα subunit (XLαs), a product of GNAS, exhibits FGF23 deficiency and hyperphosphatemia in early postnatal mice (XLKO). FGF23 elevation in response to parathyroid hormone, a stimulator of FGF23 production via cAMP, was intact in XLKO mice, while skeletal levels of protein kinase C isoforms α and δ (PKCα and PKCδ) were diminished. XLαs ablation in osteocyte-like Ocy454 cells suppressed the levels of FGF23 mRNA, inositol 1,4,5-trisphosphate (IP3), and PKCα/PKCδ proteins. PKC activation in vivo via injecting phorbol myristate acetate (PMA) or by constitutively active Gqα-Q209L in osteocytes and osteoblasts promoted FGF23 production. Molecular studies showed that the PKC activation–induced FGF23 elevation was dependent on MAPK signaling. The baseline PKC activity was elevated in bones of Hyp mice, a model of XLH. XLαs ablation significantly, but modestly, reduced serum FGF23 and elevated serum phosphate in Hyp mice. These findings reveal a potentially hitherto-unknown mechanism of FGF23 synthesis involving a G protein–coupled IP3/PKC pathway, which may be targeted to fine-tune FGF23 levels.

Dysregulated actions of the bone-derived phosphaturic hormone FGF23 result in several inherited diseases and contribute substantially to the morbidity and mortality in renal failure. Molecular mechanisms governing FGF23 production are poorly defined. Parathyroid hormone (PTH) can stimulate FGF23 production via the alpha-stimulatory G protein (Gsα) and cAMP generation. The extra-large Gα-subunit (XLαs) is partially identical to Gsα, can mimic the latter regarding cAMP generation, and can couple to the PTH receptor. However, it has been shown that XLαs acts as a Gq/11α-like protein in kidney and stimulates IP3/PKC signaling. We have found that early postnatal XLαs knockout (XLKO) mice exhibit hyperphosphatemia due to diminished FGF23 production. We aimed to elucidate the mechanism of XLαs-mediated FGF23 synthesis. 2-hour PTH injection (50nM/kg body weight) increased serum FGF23 (WT+vehicle: 520.9±9.7, WT+PTH: 2848. 5±94.0, p

To compare the accuracy of four different electronic apex locators (EALs) in detecting a position 0.5 mm short of the major foramen.The actual working length of thirty-five extracted human teeth was determined visually as 0.5 mm short of the apical foramen. After actual working length measurements, electronic working length was measured with four different EALs (Apex Pointer+, Raypex 5, Apex ID, and Raypex 6). Measurements were repeated three times by different operators. The data were analyzed using the intraclass correlation coefficient (ICC), the repeated measure analysis of variance (rANOVA) and Bonferroni post hoc tests. The significance level was set at p0.05.The mean differences between electronic and actual working length were-0.305 mm, 0.098 mm, 0.037, and 0.144 mm for the Apex Pointer+, the Raypex 5, the Apex ID, and the Raypex 6, respectively. Multiple paired comparisons (Bonferroni test) also showed the Apex Pointer+ is significantly different from the Raypex 5, Apex ID and Raypex 6 (p = 0.000, p = 0.001, and p = 0.001 respectively).All EALs showed an acceptable determination of the working length between the ranges of ± 0.5mm except for the Apex Pointer+ device, which had the lowest accuracy. Further studies may be beneficial especially to better evaluate the accuracy of the Apex Pointer+.This article shows that Apex ID, which has only recently been introduced into the market, showed an acceptable determination of the working length. Its accuracy was similar to that of Raypex 5 and 6.

Aim: To compare the accuracy of four different electronic apex locators (EALs) in detecting a position 0.5 mm short of the major foramen. Materials and methods: The actual working length of thirty-five extracted human teeth was determined visually as 0.5 mm short of the apical foramen. After actual working length measurements, electronic working length was measured with four different EALs (Apex Pointer+, Raypex 5, Apex ID, and Raypex 6). Measurements were repeated three times by different operators. The data were analyzed using the intraclass correlation coefficient (ICC), the repeated measure analysis of variance (rANOVA) and Bonferroni post hoc tests. The significance level was set at p = 0.05. Results: The mean differences between electronic and actual working length were-0.305 mm, 0.098 mm, 0.037, and 0.144 mm for the Apex Pointer+, the Raypex 5, the Apex ID, and the Raypex 6, respectively. Multiple paired comparisons (Bonferroni test) also showed the Apex Pointer+ is significantly different from the Raypex 5, Apex ID and Raypex 6 (p = 0.000, p = 0.001, and p = 0.001 respectively). Conclusion: All EALs showed an acceptable determination of the working length between the ranges of ± 0.5mm except for the Apex Pointer+ device, which had the lowest accuracy. Further studies may be beneficial especially to better evaluate the accuracy of the Apex Pointer+. Clinical significance: This article shows that Apex ID, which has only recently been introduced into the market, showed an acceptable determination of the working length. Its accuracy was similar to that of Raypex 5 and 6.

As a consequence of increasing traffic volume and mobility, road accidents have been a serious problem especially in low and middle-income countries. The number of road accidents in such countries tends to increase every year. Considering different contributing factors to the road accidents, road and its environment have played an important role. Road safety audits and road safety inspections have been worldwide used tools to monitor and to evaluate road projects and existing road sections from the safety perspective. In this study, through the evaluation of different safety auditing techniques applied in the world, a case study on a Nigerian Road Section has been implemented. The expectations from such a study are: (i) To show the main safety deficiencies of the Nigerian road sections; and (ii) To introduce a new tool to the local road authorities to further use it for monitoring their road sections. Based on this study, the audit report was prepared to summarize findings with possible countermeasures.

Pseudohypoparathyroidism type-Ia (PHP-Ia), characterized by renal proximal tubular resistance to parathyroid hormone (PTH), results from maternal mutations of GNAS that lead to loss of α-subunit of the stimulatory G protein (Gαs) activity. Gαs expression is paternally silenced in the renal proximal tubule, and this genomic event is critical for the development of PTH resistance, as patients display impaired hormone action only if the mutation is inherited maternally. The primary clinical finding of PHP-Ia is hypocalcemia, which can lead to various neuromuscular defects including seizures. PHP-Ia patients frequently do not present with hypocalcemia until after infancy, but it has remained uncertain whether PTH resistance occurs in a delayed fashion. Analyzing reported cases of PHP-Ia with documented GNAS mutations and mice heterozygous for disruption of Gnas, we herein determined that the manifestation of PTH resistance caused by the maternal loss of Gαs, ie, hypocalcemia and elevated serum PTH, occurs after early postnatal life. To investigate whether this delay could reflect gradual development of paternal Gαs silencing, we then analyzed renal proximal tubules isolated by laser capture microdissection from mice with either maternal or paternal disruption of Gnas. Our results revealed that, whereas expression of Gαs mRNA in this tissue is predominantly from the maternal Gnas allele at weaning (3 weeks postnatal) and in adulthood, the contributions of the maternal and paternal Gnas alleles to Gαs mRNA expression are equal at postnatal day 3. In contrast, we found that paternal Gαs expression is already markedly repressed in brown adipose tissue at birth. Thus, the mechanisms silencing the paternal Gαs allele in renal proximal tubules are not operational during early postnatal development, and this finding correlates well with the latency of PTH resistance in patients with PHP-Ia.

Evaluation of 2 Nickel-Titanium Instrument Systems inShaping Root Canals AbstractObjective: To evaluate root canal enlargement following mechanical shaping using 2nickel titanium rotary systems in simulated curved canals.Material and Method: Thirty simulated canals inresin blocks were divided into two experimental groups, each comprising 15resin blocks, and prepared with Twisted files (TF) and RaCe rotary files using crown-down technique. Preoperativeand postoperative photographs, taken using a digital camera, were superimposedand aberrations were recorded. The amount of resin removed was measured at 11different points, beginning at the apical terminus of the canal. Instrumentfailure, outer and inner width measurements, transportation rate, and centeringability were recorded on each central canal path and differences between groupswere statistically analyzed using Student’s t test.Results: No instrumentfracture occurred during preparation. RaCe instruments removed more materialfrom the outer canal walls in the apical section (p < 0.01) and from theinner canal walls in the middle section (p < 0.01) of the canals compared toTF. However, canals prepared with TF instruments resulted in lesstransportation (p < 0.05) in the middle section. No significant differenceswere found between the two groups in terms of centering ability in apical,middle, or coronal sections. (p >0.05).Conclusions: RaCe instrumentsremoved more resin from the outside of the apical curvature and from the inner sideof the coronal curvature compared to TF. In addition, mean transportationamount was significantly high for RaCe in middle section (i.e., coronalcurvature). Regarding canal centering ability, however, both instrumentsretained original canal geometry and performed similarly. Key words: Twisted File, RaCe, Curvedroot canals, Canal transportation, Centering ability, Ni-Ti rotarysystems KökKanallarını Şekillendirmesinde İki Nikel Titanyum Alet SistemininDeğerlendirilmesiAmaç: Simüle edilmişeğri kanallarda 2 nikel titanyum döner alet sistemi kullanılarak mekanikşekillendirme sonrası kök kanal genişlemesinin değerlendirilmesi.Gereçve Yöntem: Reçine bloklardaki otuz adet simüleedilmiş kanal, her biri 15 adet rezin bloğu içeren iki deney grubuna ayrıldı veTwisted files (TF) ve RaCe döner eğeleri kullanılarak crown-down tekniğiyleşekillendirildi. Bir dijital kamerakullanılarak çekilen preoperatif ve postoperatif fotoğraflar çakıştırıldı ve sapmalarkaydedildi. Kaldırılan rezin miktarı, kanalın apikal sonlanmasından başlayarak11 farklı noktada ölçülmüştür. Her bir kanal yolundaki dış ve iç genişlikölçümleri, transportasyon oranı, merkezde kalma yeteneği ve alet kırığıkaydedildi ve gruplar arasındaki farklar Student t testi kullanılarakistatistiksel olarak analiz edildi.Bulgular: Preparasyon sırasında alet kırılmasımeydana gelmedi. RaCe eğeleri TF’e kıyasla kanalların apikal kısımdaki dışkanal duvarlarından (p 0.05).Sonuçlar: RaCe eğeleri TF’e kıyasla, apikalkurvatürün dışından ve koronal kurvatürün iç kısmından daha fazla rezin kaldırmıştır.Ek olarak, ortalama transportasyon miktarı orta kısımda RaCe için anlamlıderecede yüksekti (yani koronal eğrilik). Bununla birlikte kanalın merkezindekalma yeteneği ile ilgili olarak, her iki enstrüman da orijinal kanalgeometrisini korudu ve kanalı benzer şekilde şekillendirdi.Anahtar kelimeler: Twisted File, RaCe, Eğri kök kanalları, Kanal transportasyonu, Merkezde kalma yeteneği, Ni-Ti döner alet sistemleri

Objective: We aimed here to evaluate the enlargement characteristics of two nickel-titanium rotary instrument systems that use two different preparation techniques, in simulated root canals under "operator-related variables" standardized conditions. Materials and Methods: A total of 40 simulated canals in resin blocks were divided into two groups as the Mtwo group for use with a single-length technique and the ProTaper instrument system group for use with crown down technique. To standardize the operator-related variables, all preparations were carried out with a computer controlled device that was developed and used previously as described in a published study. The pre- and post-operative digital images of the canals were superimposed and measured at 11 levels from the apical tip. The distances between the pre- and post-operative outer lines of the root canals were measured at both the inner and outer sides of the curve. The amount of removed material and the symmetry of the preparations were evaluated. Statistical analyses were performed with Mann-Whitney test. Results: Significantly more material was removed by Mtwo at 9 levels and by ProTaper at 2 levels (P < 0.05) while no significant difference was determined at 11 levels. The preparations made with ProTaper were more symmetrical at 4 levels while no significant difference was determined at 7 levels. Conclusions: Mtwo removed significantly more material than ProTaper at different levels of the curved root canals. Mtwo and ProTaper made symmetrical preparations and maintained the original shape of the root canal at different levels under controlled operator-related variables.

Aim. To assess and compare the water sorption, solubility and apical sealing ability of iRoot SP and three other widely used root canal sealers. Materials and methods. Solubility was assessed by immersing standardized samples of calcium silicate( iRoot SP), calcium hydroxide-(Sealapex), methacrylate resin- (EndoREZ) and epoxy resin-(AH Plus) based sealers in distilled water and measuring weight gain and weight loss at 6 h, 24 h and daily for 14 days. Roots of extracted mandibular premolars (n = 80) were prepared with 0.04-taper nickel-titanium rotary files to a final size 40. Roots were then randomly divided into four experimental groups (n = 18) and two control groups (n = 4), root canal sealers were applied and apical leakage was assessed using the fluid filtration method. Data was analyzed using Kruskal Wallis analysis of variance and Mann-Whitney U-tests, with the level of significance set at p

XLαs, a variant of the stimulatory G protein α-subunit (Gsα), can mediate receptor-activated cAMP generation and, thus, mimic the actions of Gsα in transfected cells. However, it remains unknown whether XLαs can act in a similar manner in vivo. We have now generated mice with ectopic transgenic expression of rat XLαs in the renal proximal tubule (rptXLαs mice), where Gsα mediates most actions of PTH. Western blots and quantitative RT-PCR showed that, while Gsα and type-1 PTH receptor levels were unaltered, protein kinase A activity and 25-hydroxyvitamin D 1-α-hydroxylase (Cyp27b1) mRNA levels were significantly higher in renal proximal tubules of rptXLαs mice than wild-type littermates. Immunohistochemical analysis of kidney sections showed that the sodium-phosphate cotransporter type 2a was modestly reduced in brush border membranes of male rptXLαs mice compared to gender-matched controls. Serum calcium, phosphorus, and 1,25 dihydroxyvitamin D were within the normal range, but serum PTH was ∼30% lower in rptXLαs mice than in controls (152 ± 16 vs. 222 ± 41 pg/ml; P < 0.05). After crossing the rptXLαs mice to mice with ablation of maternal Gnas exon 1 (E1m−/+), male offspring carrying both the XLαs transgene and maternal Gnas exon 1 ablation (rptXLαs/E1m−/+) were significantly less hypocalcemic than gender-matched E1m−/+ littermates. Both E1m−/+ and rptXLαs/E1m−/+ offspring had higher serum PTH than wild-type littermates, but the degree of secondary hyperparathyroidism tended to be lower in rptXLαs/E1m−/+ mice. Hence, transgenic XLαs expression in the proximal tubule enhanced Gsα-mediated responses, indicating that XLαs can mimic Gsα in vivo.

Purpose Close proximity of the inferior alveolar nerve (IAN) to the third molar roots can result in nerve injuries during extraction of third molars. Consequently, it is necessary to determine the relationship of the nerve and roots to avoid damage to the IAN. Computed tomography scans are widely used to determine the correct relationship between the IAN and lower third molars. Patients and Methods The study consisted of 10 patients with 16 lower third molars in close relationship with the IAN who were divided into a study group and a control group. The patients in the study group were treated via coronectomies performed with endodontic treatments. The patients in the control group underwent coronectomies without endodontic treatment. The patients were followed up for at least 1 year. Results We had to extract 7 of the roots because of the infection in 8 patients belonging to the study group, which were treated endodontically. Moreover, there were 3 cases of IAN damage because of the extraction in the study group. However, in the control group, no infection was determined and IAN damage was absent. Conclusion Coronectomy appears to be a reliable technique to protect the IAN from damage. This procedure has a low incidence of complications. Endodontic treatment does not affect the success of this method according to our results.

The fracture of nickel-titanium rotary instruments is a serious problem that can jeopardise the outcome of root canal treatment. The aim of this study was to compare the cyclic fatigue resistance of new and used Mtwo rotary nickel-titanium instruments in artificial canals with two different radii of curvature. Four hundred and twenty Mtwo instruments were used in the present study. Thirty new and 30 used instruments of each size were tested for cyclic fatigue in artificial canals with radii of curvature of 5 or 10 mm. Each instrument was rotated until fracture occurred and the number of cycles to fracture was calculated by multiplying time to fracture and rotational speed. Data were analysed using a t-test. According to the results of the study, radius of curvature was an important factor on cyclic fatigue resistance and clinical use significantly reduced the instrument lifespan.

Seyrek M, Vural IM, Tunca YM, Aydin C, Ulku C, Demirkaya K, Inal A, Yildiz O. The vasodilatory effect of a synthetic polymer-based root canal material on thoracic aorta. International Endodontic Journal 43, 590–599, 2010. Abstract Aim To test the hypothesis that, Epiphany, either in its mixed form or as separate components, can alter the vascular reactivity of isolated rat thoracic aorta. The possible mechanism of its vascular action was also investigated. Methodology The relaxant effect of the base, the catalyst and mixed Epiphany on isolated rat aortic rings pre-contracted with phenylephrine (PE) was tested. The aortic rings were then incubated with either nitric oxide synthase (NOS) inhibitor, cyclooxygenase (COX) inhibitor or K+ channel inhibitors; after pre-contraction with PE, relaxations to the various compounds of Epiphany were examined. In another set of experiments, to investigate the Ca2+channel antagonistic effect of the Epiphany, the effect of these compounds in Ca2+-free solution on extracellular Ca2+(CaCl2)-induced contraction in high-K+ pre-challenged rings (in K+-depolarized rings) was examined to determine whether the direct inhibition of [Ca2+] influx increase accounted for the vasodilatory effects of these compounds. For comparison, L-type Ca2+channel blocker nifedipine (1 μmol L−1), instead of Epiphany compounds, was assayed in adjacent rat aortic rings in parallel. Results The catalyst and the mixture of Epiphany induced concentration-dependent relaxations. However, the base of Epiphany did not cause relaxation in rat aorta. The relaxation responses were not significantly altered by incubation of aorta with NOS, COX and potassium channel inhibitors. Whilst nifedipine, the catalyst and the mixture of Epiphany inhibited CaCl2-induced contractions (P 0.05). Conclusion Epiphany induced relaxation of rat aorta via a calcium antagonistic effect. Provided that the vasodilatory effect elicited by Epiphany can be reversed by the circulation, its haemorrhagic potential by virtue of permanent vascular dilatation can be ignored.

WOS: 000253603600042 PubMed: 18280956 Objective. This study compared the shaping ability of Hero Shaper and RaCe instruments in simulated curved canals. Study design. Forty simulated canals in resin blocks were divided into 2 experimental groups, each comprising 20 resin blocks, and prepared with Hero Shaper and RaCe using the crown-down technique. Preoperative and postoperative photographs, recorded using a digital camera, were superimposed and aberrations were recorded. Material removal was measured at 10 points beginning 1 mm from the end point of the canal. Mean total widths, outer and inner width measurements, were determined on each central canal path and differences were statistically analyzed using Student t test. Results. The Hero Shaper and RaCe instruments removed almost the same amount of material from the inner side of the simulated canals. On the outer canal wall, the RaCe instruments removed significantly more material from the first 3 mm (P < .05). However, Hero Shaper removed more material from the middle and coronal aspects of the canal and the differences were statistically significant (P < .01). Conclusion. RaCe instruments removed more resin from the outside of the curvature at the apical thirds, while Hero Shaper removed more material from the middle and coronal thirds on the outer canal wall. Hero Shaper instruments showed better centering ability and fewer aberrations. No instrument fractures but some deformations were observed for both systems.

PTH regulates serum calcium, phosphate, and 1,25-dihydroxyvitamin D (1,25(OH)2D) levels by acting on bone and kidney. In renal proximal tubules (PTs), PTH inhibits reabsorption of phosphate and stimulates the synthesis of 1,25(OH)2D. The PTH receptor couples to multiple G proteins. We here ablated the α-subunit of the stimulatory G protein (Gsα) in mouse PTs by using Cre recombinase driven by the promoter of type-2 sodium-glucose cotransporter (GsαSglt2KO mice). GsαSglt2KO mice were normophosphatemic but displayed, relative to controls, hypocalcemia (1.19 ±0.01 vs 1.23 ±0.01 mmol/L; P < .05), reduced serum 1,25(OH)2D (59.3 ±7.0 vs 102.5 ±12.2 pmol/L; P < .05), and elevated serum PTH (834 ±133 vs 438 ±59 pg/mL; P < .05). PTH-induced elevation in urinary cAMP excretion was blunted in GsαSglt2KO mice (2- vs 4-fold over baseline in controls; P < .05). Relative to baseline in controls, PTH-induced reduction in serum phosphate tended to be blunted in GsαSglt2KO mice (−0.39 ±0.33 vs −1.34 ±0.36 mg/dL; P = .07). GsαSglt2KO mice showed elevated renal vitamin D 24-hydroxylase and bone fibroblast growth factor-23 (FGF23) mRNA abundance (∼3.4- and ∼11-fold over controls, respectively; P < .05) and tended to have elevated serum FGF23 (829 ±76 vs 632 ±60 pg/mL in controls; P = .07). Heterozygous mice having constitutive ablation of the maternal Gsα allele (E1m−/+) (model of pseudohypoparathyroidism type-Ia), in which Gsα levels in PT are reduced, also exhibited elevated serum FGF23 (474 ±20 vs 374 ±27 pg/mL in controls; P < .05). Our findings indicate that Gsα is required in PTs for suppressing renal vitamin D 24-hydroxylase mRNA levels and for maintaining normal serum 1,25(OH)2D.

The main objective of this in vitro study was to evaluate the effects of the operator's experience level and pre-flaring on the accuracy of the results of three different brands of a new generation of root canal measuring devices, as well as the comparison among them. Extracted human teeth were prepared and then actual length and electronic length measurements were made by three different operators according to a double-blind technique. Three different operators performed electronic measurements on each specimen separately with three different electronic root canal measuring devices using in vitro models. Measurements were repeated by all operators after the pre-flaring. Taking the clinical tolerance of ± 0.5 mm into account, there was no statistically significant difference between the accuracy of the instruments (P > 0.01). However, the results obtained from the Bingo electronic apex locator in pre-flared canals by the beginner operator were statistically significant (P < 0.01). All of the instruments had a clinically acceptable result at the tolerance of ± 0.5 mm. If the instruments are used in accordance with the manufacturer's instructions, experience with electronic root canal measurement is not essential. However, the operator has to be more careful when working on pre-flared canals.

Pseudohypoparathyroidism type-Ia (PHP-Ia), characterized by renal proximal tubular resistance to parathyroid hormone (PTH), results from maternal mutations of GNAS that lead to loss of α-subunit of the stimulatory G protein (Gαs) activity. Gαs expression is paternally silenced in the renal proximal tubule, and this genomic event is critical for the development of PTH resistance, as patients display impaired hormone action only if the mutation is inherited maternally. The primary clinical finding of PHP-Ia is hypocalcemia, which can lead to various neuromuscular defects including seizures. PHP-Ia patients frequently do not present with hypocalcemia until after infancy, but it has remained uncertain whether PTH resistance occurs in a delayed fashion. Analyzing reported cases of PHP-Ia with documented GNAS mutations and mice heterozygous for disruption of Gnas, we herein determined that the manifestation of PTH resistance caused by the maternal loss of Gαs, ie, hypocalcemia and elevated serum PTH, occurs after early postnatal life. To investigate whether this delay could reflect gradual development of paternal Gαs silencing, we then analyzed renal proximal tubules isolated by laser capture microdissection from mice with either maternal or paternal disruption of Gnas. Our results revealed that, whereas expression of Gαs mRNA in this tissue is predominantly from the maternal Gnas allele at weaning (3 weeks postnatal) and in adulthood, the contributions of the maternal and paternal Gnas alleles to Gαs mRNA expression are equal at postnatal day 3. In contrast, we found that paternal Gαs expression is already markedly repressed in brown adipose tissue at birth. Thus, the mechanisms silencing the paternal Gαs allele in renal proximal tubules are not operational during early postnatal development, and this finding correlates well with the latency of PTH resistance in patients with PHP-Ia.

Cementoblastoma is a rare, benign, odontogenic neoplasm of ectomesenchymal origin, representing less than 6% of all odontogenic tumors. Despite its well-known typical features, there are still controversies regarding the management of the condition. This article presents the case of a benign cementoblastoma in a 17-year-old girl. The lesion was typical and associated with the mandibular right first molar. Endodontic treatment of the involved tooth, enucleation of the cementoblastoma, and apicoectomy of the affected roots were performed. Removal of the tumor while preserving the associated tooth resulted in normal osseous healing and no evidence of recurrence after one year. Based on the findings of the current report, it can be suggested that, in properly selected cases, it is possible to remove cementoblastomas that affect molars without extracting the involved teeth.

The prime concern of transportation planners in developing countries is how to collect and transfer data into models as simple and as effective as possible and obtain solutions in the shortest time. In this study, a methodology which utilizes multivariate statistical analysis techniques for travel estimation is presented. The two simple and convenient techniques namely Cluster Analysis and Principal Component Analysis, are used for the evaluation of available data. The traffic demand is expressed as a function of principal components which are determined independently as a small set of variables to represent total system variability. A stepwise regression analysis is carried out to derive the traffic demand‐principal component relationship. The proposed methodology is then applied to Southeastern Anatolia Regional Development Project in Turkey.

The fracture of nickel-titanium rotary instruments is a serious problem that can jeopardise the outcome of root canal treatment. The aim of this study was to compare the cyclic fatigue resistance of new and used Mtwo rotary nickel-titanium instruments in artificial canals with two different radii of curvature. Four hundred and twenty Mtwo instruments were used in the present study. Thirty new and 30 used instruments of each size were tested for cyclic fatigue in artificial canals with radii of curvature of 5 or 10 mm. Each instrument was rotated until fracture occurred and the number of cycles to fracture was calculated by multiplying time to fracture and rotational speed. Data were analysed using a t-test. According to the results of the study, radius of curvature was an important factor on cyclic fatigue resistance and clinical use significantly reduced the instrument lifespan.

Patients with McCune-Albright syndrome (MAS), characterized primarily by hyperpigmented skin lesions, precocious puberty, and fibrous dyslasia of bone, carry postzygotic heterozygous mutations of GNAS causing constitutive cAMP signaling. GNAS encodes the α-subunit of the stimulatory G protein (Gsα), as well as a large variant (XLαs) derived from the paternal allele. The mutations causing MAS affect both GNAS products, but whether XLαs, like Gsα, can be involved in the pathogenesis remains unknown. Here, we investigated biopsy samples from four previously reported and eight new patients with MAS. Activating mutations of GNAS (Arg201 with respect to the amino acid sequence of Gsα) were present in all the previously reported and five of the new cases. The mutation was detected within the paternally expressed XLαs transcript in five and the maternally expressed NESP55 transcript in four cases. Tissues carrying paternal mutations appeared to have higher XLαs mRNA levels than maternal mutations. The human XLαs mutant analogous to Gsα-R201H (XLαs-R543H) showed markedly higher basal cAMP accumulation than wild-type XLαs in transfected cells. Wild-type XLαs demonstrated higher basal and isoproterenol-induced cAMP signaling than Gsα and co-purified with Gβ1γ2 in transduced cells. XLαs mRNA was measurable in mouse calvarial cells, with its level being significantly higher in undifferentiated cells than those expressing preosteoblastic markers osterix and alkaline phosphatase. XLαs mRNA was also expressed in murine bone marrow stromal cells and preosteoblastic MC3T3-E1 cells. Our findings are consistent with the possibility that constitutive XLαs activity adds to the molecular pathogenesis of MAS and fibrous dysplasia of bone.

Introduction: The aim of this study was to evaluate the push-out bond strength of iRoot SP (Innovative Bioceramix, Vancouver, Canada) and compare it with that of other widely used root canal sealers. Methods: Sixty extracted human maxillary canines were sectioned transversally below the cement-enamel junction to obtain 120 4-mm-thick dentin disks that were randomly divided into four groups (n = 30) for treatment with one of four different root-canal sealers (iRoot SP, AH Plus [Dentsply DeTrey GmbH, Konstanz, Germany], Sealapex [SybronEndo Corporation, Orange, CA], EndoREZ [Ultradent Inc, South Jordan, UT]). Standardized cavities were prepared to simulate root canals, cavities were filled with sealer material, and push-out bond-strength testing was performed using a universal testing machine. Failure modes were assessed quantitatively under a stereomicroscope and morphologically under a scanning electron microscope. Statistical analysis was performed using one-way analysis of variance and the post hoc Tukey test, with the significance level set at 0.05. Results: Bond strengths of iRoot SP and AH Plus were significantly higher than those of Sealapex and EndoREZ. There was no significant difference between the bond strength of iRoot SP and AH Plus (p = 0.274). Conclusions: iRoot SP and AN Plus performed similarly and better than EndoREZ and Sealapex in terms of bond strength. (J Endod 2010;36:2000 -2002)

An autosomal recessive form of hypophosphatemia (ARHP) was recently shown to be caused by homozygous mutations in DMP1, the gene encoding dentin matrix protein-1 (DMP-1), a non-collagenous bone matrix protein with an important role in the development and mineralization of bone and teeth. Here, we describe a previously not reported consanguineous ARHP kindred in which the three affected individuals carry a novel homozygous DMP-1 mutation. The index case presented at the age of 3 years with bowing of his legs and showed hypophosphatemia due to insufficient renal phosphate retention. Serum alkaline phosphatase activity was elevated, with initially normal PTH. FGF23 was inappropriately normal at an older age while being treated with oral phosphate and 1,25(OH)(2)D. Similar clinical and biochemical findings, except for elevated FGF23 levels, were present in his 16-month-old brother and his 12.5-year-old female cousin; the parents of the three affected children are first-degree cousins. Nucleotide sequence analysis was performed on PCR-amplified exons encoding DMP-1 and flanking intronic regions. A novel homozygous frame-shift mutation (c.485Tdel; p.GLu163ArgfsX53) in exon 6 resulting in a premature stop codon was identified in all effected individuals. The parents and available unaffected siblings were heterozygous for c.485Tdel. Tooth growth and shape were normal for the index case, his affected brother and cousin, but their permanent and deciduous teeth displayed enlarged pulp chambers. The identified genetic mutation underscores the importance of DMP-1 mutations in the pathogenesis of ARHP. Furthermore, DMP-1 mutations appear to contribute, through yet unknown mechanisms, to tooth development. (C) 2009 Elsevier Inc. All rights reserved.

WOS: 000274956600046 PubMed: 20219578 Objective. The aim of this study was to evaluate cyclic fatigue resistance of used and new RaCe rotary nickel-titanium instruments. Study design. Forty RaCe (FKG Dentaire, La-Chaux-de-Fonds, Switzerland) instruments of sizes 30/.06, 30/.02, 25/.04, and 25/.02 were selected and divided into 2 groups: group A = 20 new instruments; group B = 20 used instruments. In group B, each instrument was used for shaping 5 curved molar root canals. Cyclic fatigue testing of new and used instruments was performed using a device that allowed the instruments to rotate freely inside a stainless steel artificial canal. Data were analyzed using t test to determine any statistical significance between used and new instruments of the same file size. Results. For all sizes, new instruments were more resistant to failure then the used ones (P < .05). A reduction in lifespan was observed ranging from 18% (30/.06) to 51% (25/.02). Conclusion. The results showed that clinical use significantly reduced cyclic fatigue resistance of RaCe rotary instruments compared with new ones. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010; 109: e131-e134)

GNAS gives rise to multiple imprinted gene products, including the alpha-subunit of the stimulatory G protein (Gs(alpha)) and its variant XL(alpha)s. Based on genomic sequence, the translation of XL(alpha)s begins from the middle of a long open reading frame, suggesting the existence of an N-terminally extended variant termed extralarge XLalphas (XXL(alpha)s). Although XXL(alpha), like Gs(alpha) and XL(alpha)s, would be affected by most disease-causing GNAS mutations, its authenticity and biological significance remained unknown. Here we identified a mouse cDNA clone that comprises the entire open reading frame encoding XXL(alpha)s. Whereas XXL(alpha)s mRNA was readily detected in mouse heart by RT-PCR, it appeared virtually absent in insulinoma-derived INS-1 cells. By Northern blots and RT-PCR, XXL(alpha)s mRNA was detected primarily in the mouse brain, cerebellum, and spleen. Immunohistochemistry using a specific anti-XXL(alpha)s antibody demonstrated XXL(alpha)s protein in multiple brain areas, including dorsal hippocampus and cortex. In transfected cells, full-length human XXL(alpha)s was localized to the plasma membrane and mediated isoproterenol- and cholera toxin-stimulated cAMP accumulation. XXL(alpha)s-R844H, which bears a mutation analogous to that in the constitutively active Gs(alpha) mutant Gs(alpha)-R201H (gsp oncogene), displayed elevated basal signaling. However, unlike Gs(alpha)-R201H, which mostly remains in the cytoplasm, both XXL(alpha)s-R844H and a constitutively active XL(alpha)s mutant localized to the plasma membrane. Hence, XXL(alpha)s is a distinct GNAS product and can mimic Gs(alpha), but the constitutively active XXL(alpha)s and Gs(alpha) mutants differ from each other regarding subcellular targeting. Our findings suggest that XXL(alpha)s deficiency or hyperactivity may contribute to the pathogenesis of diseases caused by GNAS mutations.

Widespread use of rotary nickel-titanium systems has caused manufacturers to produce gutta-percha cones that match the taper of the canals prepared with these systems. Obturations with these cones may provide 3-dimensional obturation of the root canal in less time. The aim of this study was to use a fluid filtration method to compare the apical sealing ability of matched-taper single-cone, Thermafil and lateral condensation obturations.Sixty-six extracted human lower premolar teeth were instrumented to size F3 with ProTaper instruments. The teeth were divided into 3 groups and obturated with matched-taper single-cone, Thermafil and lateral condensation techniques. AH Plus was used as a sealer. Six teeth were used as positive and negative controls. A fluid filtration system was used to evaluate the apical seal. Measurements were made at 2-minute intervals for 8 minutes and the average of these values was recorded. One-way analysis of variance test was used for statistical analysis.Mean leakage values for the lateral condensation, single-cone and Thermafil groups were 0.49 +/- 0.37 microL min(-1), 0.39 +/- 0.24 microL min(-1) and 0.44 +/- 0.25 microL min(-1), respectively. The difference between the groups was not statistically significant (p0.05).The apical sealing ability of matched-taper single-cone obturation was comparable with that of lateral condensation and Thermafil techniques.

Intrusive luxation is a serious dental injury that causes damage to the pulp and supporting structures of a tooth because of its dislocation into the alveolar process. This paper presents the case of the re-eruption of a severely intruded immature permanent incisor with a crown-root fracture. A 9-year-old boy was referred to the clinic 1 day after a fall. Clinical and radiographic examinations revealed intrusive luxation of the immature left permanent incisor and a crown-root fracture without pulp exposure. Palatal gingivectomy was done 2 weeks later to facilitate re-eruption. Root canal therapy with intracanal calcium hydroxide paste was initiated during the first month owing to severe spontaneous pain. Six months later, the tooth re-erupted to a normal position, after which root canal obturation and a final esthetic restoration were done. The present case demonstrates the possibility of obtaining re-eruption of intruded immature permanent teeth with interim medication (calcium hydroxide) in the root canal.

WOS: 000255344300020 PubMed: 18329912 Objective. The aim of this study was to investigate the effect of sodium hypochlorite immersion on the surface characteristics of RaCe rotary nickel-titanium instruments using atomic force microscopy (AFM). Study design. Four new RaCe instruments were used in this study (two 30.06 and two 30.02). One 30.06 and one 30.02 instrument were immersed in sodium hypochlorite solution for 5 min. Surface topography of the instruments was evaluated using the AFM. The instruments were analyzed on 11 points along a 3-mm section. Root mean square (RMS) values were used to compare the topographic deviations. The data were analyzed using Student t test. Results. Mean RMS values for NaOCl measurements were higher than the measurements on new files, and the difference was statistically significant (P

WOS: 000251677300031 PubMed: 17904394 Objective. This study compared the cyclic fatigue resistance of ProTaper rotary nickel-titanium (NiTi) files in artificial canals with 2 different radii of curvature. Study design. One hundred ProTaper rotary instruments were used in this study. Twenty files of each size (S1, S2, F1, F2, and F3) were tested. Cyclic fatigue testing was performed using a device that allowed the instruments to rotate freely inside stainless steel artificial canals with radii of curvature of 5 and 10 mm. The number of cycles to fracture was recorded for each file and the data were analyzed using a t-test. Results. The 5-mm radius group had significantly fewer cycles to fracture than the 10-mm radius group for all file sizes. For sizes F2 and F3, the difference between the 5 and 10-mm radius groups was highly significant (P < .001). For the 10-mm group, the difference between S1 and F3 was significant (P < .05). For the more abrupt 5-mm radius group, the difference between S1-F2, S2-F2, and F1-F2 was statistically significant. The difference between S1-F3, S2-F3, and F1-F3 was highly significant (P < .001). Conclusion. Cyclic fatigue resistance of ProTaper instruments was dependent on both instrument size and radius of curvature. Especially larger-size instruments should be used with great care in curved canals.

Objective. This study aimed to test the hypothesis that aggressive dentin removal through greater-tapered instrumentation reduces the intracanal bacteria more effectively than conservative dimension instrumentation. Material and methods. Twenty extracted human lower premolar teeth were used. After extirpation of the pulps, the teeth were autoclaved and immersed in a broth inoculated with Enterococcus faecalis and incubated for 7 days to allow infection of the dentinal tubules. The teeth were divided into 2 experimental groups, each comprising 10 teeth. The teeth were instrumented either with ProTaper or with Hero Shaper nickel-titanium rotary instrumentation techniques. It was calculated that ProTaper theoretically has the potential to remove at least twice the dentin volume compared with Hero Shaper. The apical preparation was standardized to file size 30. Saline solution was used for irrigation. Bacteriological samples were taken before and after instrumentation and plated onto tryptic soy agar, and the reduction in numbers was calculated. Results. Both instrumentation techniques significantly reduced the number of bacteria in the root canal (p < 0.05). Reduction in absolute bacterial numbers was up to 98%. There was no statistically significant difference between the two techniques. Conclusions. Preparation with an instrumentation technique removing substantial amounts of dentin did not reduce the intracanal bacteria more effectively than a more conservative instrumentation technique.

WOS: 000250764300016 PubMed: 17963958 The purpose of this study was to evaluate the topography of new and used ProTaper rotary nickel-titanium (NiTi) instruments by using atomic force microscope. Four new and four used size S1, S2, F1, and F2 instruments were selected for this study. New and used instruments were analyzed on 11 points along a 3-mm section at the tip of the instrument. Quantitative measurements according to the topographic deviations (root mean square) were recorded. Data were analyzed by paired samples t test. Mean root mean square values for used ProTaper instruments were higher than the new ones, and the difference between them was statistically significant. The results of this study showed that used ProTaper instruments demonstrated more surface deformation and wear.

Mineral trioxide aggregate (MTA) is being advocated for vital pulp therapy. In the case of direct pulp capping, hemorrhage control is an important step on success, but little is known about the effect of MTA on pulpal bleeding. In addition, there has been a lack of information on the effect of MTA on smooth muscle contraction, such as can occur in the blood vessels of dental pulp. The present study assessed the vascular effects of MTA, using the rat aortic ring preparations as a tissue model. MTA (100–500 mg) induced dose–dependent contraction in rat thoracic aorta. The contractile effect of MTA was blocked by calcium channel blocker nifedipine (1 μM). These data suggest that the vasoconstrictor property of MTA is related to calcium influx and it may allow proper control of hemorrhage which is critical for the success of any pulp-capping treatment.

Background Chemical and mechanic iritations may play causative role in development of lichenoid reactions in oral mucosa, similar to skin, in predisposed patients. It has recently been reported that lichenoid reactions and Wickham striae with papular/reticular characteristics are observed in mucosal regions which are in direct contact with amalgam restorations (1). A 38-year-old male patient admitted initially to the Department of Oral Diagnosis and Radiology, chiefly complaining of bilateral buccal pain and itching. In his intraoral inspection, hyperkeratotic white lesions at his molar teeth level at both right and left buccal mucosa were observed. The purpose of this study is to find out the nature and decide on the management of these buccal lesions. Methods In dental inspection of the patient, large amalgam restorations and white lesions in buccal surface in direct contact with amalgam were observed in left first and second, and right second molar teeth region. A 4-mm punch biopsy from buccal mucosa was performed. In addition, a skin patch test with amalgam was done in back region of the patient. Results In punch biopsy, histopathological features were compatible with lichenoid mucositis. In addition, skin patch test results indicated a very strong positive reaction to amalgam. The lesion healed up after replacement of restorations with composite filling material. The patient, his family and his dental practitioner were strictly advised to use alternative restorative materials in case of a need for restoration. Conclusions Amalgam and its components may cause type IV hypersensitivity reactions (1) and, very unusually, immediate hypersensitivity (2). The clinician should be aware of all possible pathological etiologies of white lesions. If there is any doubt about the diagnosis and management of an anusual oral lesion, referral to appropriate specialists is mandatory.