Glucocorticoids in Vivo Induce Both Insulin Hypersecretion and Enhanced Glucose Sensitivity of Stimulus-Secretion Coupling in Isolated Rat Islets

Although glucocorticoids are widely used as antiinflammatory agents in clinical therapies, they may cause serious side effects that include insulin resistance and hyperinsulinemia. To study the potential functional adaptations of the islet of Langerhans to in vivo glucocorticoid treatment, adult Wistar rats received dexamethasone (DEX) for 5 consecutive days, whereas controls (CTL) received only saline. The analysis of insulin release in freshly isolated islets showed an enhanced secretion in response to glucose in DEX-treated rats. The study of Ca(2+) signals by fluorescence microscopy also demonstrated a higher response to glucose in islets from DEX-treated animals. However, no differences in Ca(2+) signals were found between both groups with tolbutamide or KCl, indicating that the alterations were probably related to metabolism. Thus, mitochondrial function was explored by monitoring oxidation of nicotinamide dinucleotide phosphate autofluorescence and mitochondrial membrane potential. Both parameters revealed a higher response to glucose in islets from DEX-treated rats. The mRNA and protein content of glucose transporter-2, glucokinase, and pyruvate kinase was similar in both groups, indicating that changes in these proteins were probably not involved in the increased mitochondrial function. Additionally, we explored the status of Ca(2+)-dependent signaling kinases. Unlike calmodulin kinase II, we found an augmented phosphorylation level of protein kinase C alpha as well as an increased response of the phospholipase C/inositol 1,4,5-triphosphate pathway in DEX-treated rats. Finally, an increased number of docked secretory granules were observed in the beta-cells of DEX animals using transmission electron microscopy. Thus, these results demonstrate that islets from glucocorticoid-treated rats develop several adaptations that lead to an enhanced stimulus-secretion coupling and secretory capacity. (Endocrinology 151: 85-95, 2010)

Sensitivity of complex networks measurements

Complex networks obtained from real-world networks are often characterized by incompleteness and noise, consequences of imperfect sampling as well as artifacts in the acquisition process. Because the characterization, analysis and modeling of complex systems underlain by complex networks are critically affected by the quality and completeness of the respective initial structures, it becomes imperative to devise methodologies for identifying and quantifying the effects of the sampling on the network structure. One way to evaluate these effects is through an analysis of the sensitivity of complex network measurements to perturbations in the topology of the network. In this paper, measurement sensibility is quantified in terms of the relative entropy of the respective distributions. Three particularly important kinds of progressive perturbations to the network are considered, namely, edge suppression, addition and rewiring. The measurements allowing the best balance of stability (smaller sensitivity to perturbations) and discriminability (separation between different network topologies) are identified with respect to each type of perturbation. Such an analysis includes eight different measurements applied on six different complex networks models and three real-world networks. This approach allows one to choose the appropriate measurements in order to obtain accurate results for networks where sampling bias cannot be avoided-a very frequent situation in research on complex networks.

Dentin hypersensitivity clinical study comparing LILT and LEDT keeping the same irradiation parameters

Dentin hypersensitivity is a common condition associated with high dental pain. A new LED-based (light emitting diode) light source has been used as an experimental tool in some studies. Purpose: The main objective was to compare these two light sources emitting in the same spectral band (red from 625 to 660 nm) to promote pain relief. Material and methods: A total of 6 sessions were accomplished, being three irradiation sessions and three follow-up sessions. This single-blind study compared a control group (Placebo) and two other groups with different equipments: low laser intensity treatment (LILT) and a light emitting diode system treatment (LEDT). Results: The results showed that there is no statistical difference between LILT and LEDT groups, however, both were better than control group (p=0.01) in terms of treatment efficiency; there is no difference between the second and the third sessions for both treatment, it means that the third session was not necessary; finally, the improvement at the end of the entire research (follow up care of 30 days) was very expressive in comparison to pre-treatment situation for all teeth (p=0.01). Conclusion: LILT and LEDT were equally effective to treat dentine hypersensitivity, a 3rd treatment session was not necessary/two sessions are enough.

Effect of light-curing units on push-out fiber post bond strength in root canal dentin

The purpose of this study was to evaluate the effectiveness of different light-curing units on the bond strength (push-out) of glass fiber posts in the different thirds of the root (cervical, middle and apical) with different adhesive luting resin systems (dual-cure total-etch; dual-cured and self-etch bonding system; and dual-cure self-adhesive cements), Disks of the samples (n = 144) were used, with approximately 1 mm of thickness of 48 bovine roots restored with glass fiber posts, that were luted with resin cements photo-activated by halogen LCU (QTH, Optilux 501) and blue LED (Ultraled), with power densities of 600 and 550 mW/cm(2), respectively. A universal testing machine (MTS 810 Material Test System) was used with a 1 mm diameter steel rod at cross-head speed of 0.5 mm/min until post extrusion, with load cell of 50 kg, for evaluation of the push-out strength in the different thirds of each sample. The push-out strength values in kgf were converted to MPa and analyzed through Analysis of Variance and Tukey`s test, at significance level of 5%. The results showed that there were no statistical differences between the QTH and LED LCUs. The self-adhesive resin cement had lower values of retention. The total-etch and self-adhesive system resin cements seem to be a possible alternative for glass fiber posts cementation into the radicular canal and the LED LCU can be applied as an alternative to halogen light on photo-activation of dual-cured resin cements.

Correlation between thermoluminescence sensitivity and crystallization temperatures of quartz: Potential application in geothermometry

The thermoluminescence (TL) characteristics of quartz are highly dependent of its thermal history. Based on the enhancement of quartz luminescence occurred after heating, some authors proposed to use quartz TL to recover thermal events that affected quartz crystals. However, little is know about the influence of the temperature of quartz crystallization on its TL characteristics. In the present study, we evaluate the TL sensitivity and dose response curves of hydrothermal and metamorphic quartz with crystallization temperatures from 209 +/- 15 to 633 +/- 27 degrees C determined through fluid inclusion and mineral chemistry analysis. The studied crystals present a cooling thermal history, which allow the acquiring of their natural TL without influence of heating after crystallization. The TL curves of the studied samples present two main components formed by different peaks overlapped around 110 C and 200-400 degrees C. The TL sensitivity in the 200-400 degrees C region increases linearly with the temperature of quartz crystallization. No relationship was observed between temperatures of quartz crystallization and saturation doses (<100 Gy). The elevated TL sensitivity of the high temperature quartz is attributed to the control exerted by the temperature of crystallization on the substitution of Si(4+) by ions such as Al(3+) and Ti(4+), which produce defects responsible for luminescence phenomena. The linear relationship observed between TL in the 200-400 degrees C region and crystallization temperature has potential use as a quartz geothermometer. The relative abundance of quartz in the earth crust and the easiness to measure TL are advantageous in relation to geothermometry methods based on chemistry of other minerals. (C) 2010 Elsevier Ltd. All rights reserved.

Thermal history versus sedimentary history: OSL sensitivity of quartz grains extracted from rocks and sediments

The optically stimulated luminescence (OSL) sensitivity of quartz has a significant influence on luminescence dating procedures. Furthermore, identifying the natural controls of quartz OSL sensitivity is an important step towards new applications of OSL in geology such as provenance tracing. We evaluate the OSL sensitivity (total and the proportion of the informally assigned fast, medium and slow components) of single grains of quartz extracted from 10 different igneous and metamorphic rocks with known formation conditions; and from fluvial and coastal sediments with different sedimentary histories and known source rocks. This sample suite allows assessment of the variability of the OSL sensitivity of single quartz grains with respect to their primary origin and sedimentary history. We observed significant variability in the OSL sensitivity of grains within all studied rock and sediment samples, with the brightest grains of each sample being those dominated by the fast component. Quartz from rocks formed under high temperature (> 500 degrees C) conditions, such as rhyolites and metamorphic rocks from the amphibolite facies, display higher OSL sensitivity. The OSL sensitivity of fluvial sediments which have experienced only a short transport distance is relatively low. These sediments show a small increase in OSL sensitivity downstream, mainly due to a decreasing fraction of ""dim"" grains. The quartz grains from coastal sands present very high sensitivity and variability, which is consistent with their long sedimentary history. The high variability of the OSL sensitivity of quartz from coastal sands is attributed more to the mixture of grains with distinct sedimentary histories than to the provenance from many types of source rocks. The temperature of crystallization and the number of cycles of burial and solar exposure are suggested as the main natural factors controlling the OSL sensitivity of quartz grains. The increase in OSL sensitivity due to cycles of erosion and deposition surpasses the sensitivity inherited from the source rock, with this increase being mainly related to the sensitization of fast OSL components. The discrimination of grains with different sedimentary histories through their OSL sensitivities can allow the development of quantitative provenance methods based on quartz. (C) 2010 Elsevier B.V. All rights reserved.

Vision in click beetles (Coleoptera: Elateridae): pigments and spectral correspondence between visual sensitivity and species bioluminescence emission

Among lampyrids, intraspecific sexual communication is facilitated by spectral correspondence between visual sensitivity and bioluminescence emission from the single lantern in the tail. Could a similar strategy be utilized by the elaterids (click beetles), which have one ventral abdominal and two dorsal prothoracic lanterns? Spectral sensitivity [S(lambda)] and bioluminescence were investigated in four Brazilian click beetle species Fulgeochlizus bruchii, Pyrearinus termitilluminans, Pyrophorus punctatissimus and P. divergens, representing three genera. In addition, in situ microspectrophotometric absorption spectra were obtained for visual and screening pigments in P. punctatissimus and P. divergens species. In all species, the electroretinographic S(lambda) functions showed broad peaks in the green with a shoulder in the near-ultraviolet, suggesting the presence of short- and long-wavelength receptors in the compound eyes. The long-wavelength receptor in Pyrophorus species is mediated by a P540 rhodopsin in conjunction with a species-specific screening pigment. A correspondence was found between green to yellow bioluminescence emissions and its broad S(lambda) maximum in each of the four species. It is hypothesized that in elaterids, bioluminescence of the abdominal lantern is an optical signal for intraspecifc sexual communication, while the signals from the prothoracic lanterns serve to warn predators and may also provide illumination in flight.

Estimation of genetic variance for macro- and micro-environmental sensitivity using double hierarchical generalized linear models

Background: Genetic variation for environmental sensitivity indicates that animals are genetically different in their response to environmental factors. Environmental factors are either identifiable (e.g. temperature) and called macro-environmental or unknown and called micro-environmental. The objectives of this study were to develop a statistical method to estimate genetic parameters for macro- and micro-environmental sensitivities simultaneously, to investigate bias and precision of resulting estimates of genetic parameters and to develop and evaluate use of Akaike’s information criterion using h-likelihood to select the best fitting model. Methods: We assumed that genetic variation in macro- and micro-environmental sensitivities is expressed as genetic variance in the slope of a linear reaction norm and environmental variance, respectively. A reaction norm model to estimate genetic variance for macro-environmental sensitivity was combined with a structural model for residual variance to estimate genetic variance for micro-environmental sensitivity using a double hierarchical generalized linear model in ASReml. Akaike’s information criterion was constructed as model selection criterion using approximated h-likelihood. Populations of sires with large half-sib offspring groups were simulated to investigate bias and precision of estimated genetic parameters. Results: Designs with 100 sires, each with at least 100 offspring, are required to have standard deviations of estimated variances lower than 50% of the true value. When the number of offspring increased, standard deviations of estimates across replicates decreased substantially, especially for genetic variances of macro- and micro-environmental sensitivities. Standard deviations of estimated genetic correlations across replicates were quite large (between 0.1 and 0.4), especially when sires had few offspring. Practically, no bias was observed for estimates of any of the parameters. Using Akaike’s information criterion the true genetic model was selected as the best statistical model in at least 90% of 100 replicates when the number of offspring per sire was 100. Application of the model to lactation milk yield in dairy cattle showed that genetic variance for micro- and macro-environmental sensitivities existed. Conclusion: The algorithm and model selection criterion presented here can contribute to better understand genetic control of macro- and micro-environmental sensitivities. Designs or datasets should have at least 100 sires each with 100 offspring.

Simplified follow-up after medical abortion using a low-sensitivity urinary pregnancy test and a pictorial instruction sheet in Rajasthan, India : study protocol and intervention adaptation of a randomised control trial

The World Health Organisation suggests that simplification of the medical abortion regime will contribute to an increased acceptability of medical abortion, among women as well as providers. It is expected that a home-based follow-up after a medical abortion will increase the willingness to opt for medical abortion as well as decrease the workload and service costs in the clinic. Trial design The study is a randomised, controlled, non-superiority trial . Methods Women screened to participate in the study are those with unwanted pregnancies and gestational ages equal to or less than nine weeks. Eligible women randomised to the home-based assessment group will use a low-sensitivity pregnancy test and a pictorial instruction sheet at home, while the women in the clinic follow-up group will return to the clinic for routine follow-up carried out by a doctor. The primary objective of the study is to evaluate the effectiveness of home-based assessment using a low-sensitivity pregnancy test and a pictorial instruction sheet 10-14 days after an early medical abortion. Providers or research assistants will not be blinded during outcome assessment. To ensure feasibility of the self-assessment intervention an adaption phase took place at the selected study sites before study initiation. This was to optimise and tailor-make the intervention and the study procedures and resulted in the development of the pictorial instruction sheet for how to use the low-sensitivity pregnancy test and the danger signs after a medical abortion. Discussion In this paper, we will describe the study protocol for a randomised control trial investigating the efficacy of simplified follow-up in terms of home-based assessment, 10-14 days after a medical abortion. Moreover, a description of the adaptation phase is included for a better understanding of the implementation of the intervention in a setting where literacy is low and the road-connections are poor. Trial registration: Clinicaltrials.gov NCT01827995. Registered 04 May 2013

Elevation in tanis expression alters glucose metabolism and insulin sensitivity in H4IIE cells

Increased hepatic glucose output and decreased glucose utilization are implicated in the development of type 2 diabetes. We previously reported that the expression of a novel gene, Tanis, was upregulated in the liver during fasting in the obese/diabetic animal model Psammomys obesus. Here, we have further studied the protein and its function. Cell fractionation indicated that Tanis was localized in the plasma membrane and microsomes but not in the nucleus, mitochondria, or soluble protein fraction. Consistent with previous gene expression data, hepatic Tanis protein levels increased more significantly in diabetic P. obesus than in nondiabetic controls after fasting. We used a recombinant adenovirus to increase Tanis expression in hepatoma H4IIE cells and investigated its role in metabolism. Tanis overexpression reduced glucose uptake, basal and insulin-stimulated glycogen synthesis, and glycogen content and attenuated the suppression of PEPCK gene expression by insulin, but it did not affect insulin-stimulated insulin receptor phosphorylation or triglyceride synthesis. These results suggest that Tanis may be involved in the regulation of glucose metabolism, and increased expression of Tanis could contribute to insulin resistance in the liver.

Effect of creatine ingestion on glucose tolerance and insulin sensitivity in men

Purpose: This study investigated whether acute (5 d) and/or short-term (28 d) creatine (Cr) ingestion altered glucose tolerance or insulin action in healthy, untrained men (aged 26.9 ± 5.7 yr; SD). Methods : Subjects were randomly allocated to either a Cr (N = 8) or placebo group (N = 9) and were tested in the control condition (presupplementation), and after 5 and a further 28 d of supplementation. The Cr group ingested 20 g and 3 g·d-1 of Cr for the first 5 and following 28 d, respectively. The placebo group ingested similar amounts of glucose over the same time period. During each testing period, subjects underwent an oral glucose tolerance test (OGTT) to determine insulin sensitivity, and six subjects from each group underwent a muscle biopsy before each OGTT. Results : Cr supplementation resulted in an increased (P < 0.05) muscle TCr content after both the acute and short-term loading phase compared with placebo. Neither acute nor short-term Cr supplementation influenced skeletal muscle glycogen content, glucose tolerance, or measures of insulin sensitivity. Conclusions: These findings demonstrated that acute Cr supplementation (20 g·d-1 for 5 d) followed by short-term Cr supplementation (3 g·d-1 for 28 d) did not alter insulin action in healthy, active untrained men.

Spatio-temporal selectivity of loss of colour and luminance contrast sensitivity with mutiple sclerosis and optic neuritis

Colour and luminance-contrast thresholds were measured in the presence of dynamic Random Luminance-contrast Masking (RLM) in individuals who had had past diagnoses of optic neuritis (ON) some of whom have progressed to a diagnosis of multiple sclerosis (MS). To explore the spatio-temporal selectivity of chromatic and luminance losses in MS/ON, thresholds were measured using three different sizes and modulation rates of the RLM displays: small checks modulating slowly, medium-sized checks with moderate modulation and large checks modulating rapidly. The colour of the chromatic stimuli used were specified in a cone-excitation space to measure relative impairments in red–green and blue–yellow chromatic channels. These observers showed chromatic thresholds along the L/(L + M) axis that were higher than those along the S-cone axis for all display sizes/modulation rates and both red-green and blue-yellow colour thresholds were higher than luminance-contrast thresholds. The principal change in thresholds with spatio-temporal changes in the display was a reduction in thresholds for L/(L + M) and S-cones with increasing check size and modulation rate. However, luminance contrast thresholds did not change with display size/rate. These results are consistent with MS/ON selectively affecting processing in colour pathways rather than in the magnocellular pathway, and that within the colour pathways neurones with opposed L- and M-cone inputs are more damaged than colour-opponent neurons with input from S-cones.