Baroreflex sensitivity and oxidative stress in the LDL receptor knockout mice

This study alms at observing the effect of low-density lipoprotein (LDL) receptor deficiency in cholesterol blood levels, baroreflex sensitivity (BRS), nitric oxide (NO) bioavailability, and oxidative stress. The lack of LDL receptors in mice significantly increased the cholesterol blood levels (179 +/- 35 vs. 109 +/- 13 mg/dL) in the knockout (KO) mice compared to control. There was no difference in basal mean arterial pressure and heart rate between the groups. However, in KO mice the BRS was significantly attenuated and the antioxidant enzyme activities, measured in erythrocytes and heart, were significantly decreased. On the other hand, the oxidative damage measured by chemiluminescence and carbonyls was increased, while total plasma nitrate levels were lower in KO mice, indicating a decrease in NO availability. In conclusion, these results indicate that the lack of LDL receptor increased cholesterol blood levels, induced oxidative stress and decreased BRS. (C) 2008 Elsevier GmbH. All rights reserved.

Genetic and Functional Evidence Implicating DLL1 as the Gene That Influences Susceptibility to Visceral Leishmaniasis at Chromosome 6q27

Background. Visceral leishmaniasis (VL) is caused by Leishmania donovani and Leishmania infantum chagasi. Genome-wide linkage studies from Sudan and Brazil identified a putative susceptibility locus on chromosome 6q27. Methods. Twenty-two single-nucleotide polymorphisms (SNPs) at genes PHF10, C6orf70, DLL1, FAM120B, PSMB1, and TBP were genotyped in 193 VL cases from 85 Sudanese families, and 8 SNPs at genes PHF10, C6orf70, DLL1, PSMB1, and TBP were genotyped in 194 VL cases from 80 Brazilian families. Family-based association, haplotype, and linkage disequilibrium analyses were performed. Multispecies comparative sequence analysis was used to identify conserved noncoding sequences carrying putative regulatory elements. Quantitative reverse-transcription polymerase chain reaction measured expression of candidate genes in splenic aspirates from Indian patients with VL compared with that in the control spleen sample. Results. Positive associations were observed at PHF10, C6orf70, DLL1, PSMB1, and TBP in Sudan, but only at DLL1 in Brazil (combined P = 3 x 10(-4) at DLL1 across Sudan and Brazil). No functional coding region variants were observed in resequencing of 22 Sudanese VL cases. DLL1 expression was significantly (P = 2 x 10(-7)) reduced (mean fold change, 3.5 [SEM, 0.7]) in splenic aspirates from patients with VL, whereas other 6q27 genes showed higher levels (1.27 x 10(-6) < P < .01) than did the control spleen sample. A cluster of conserved noncoding sequences with putative regulatory variants was identified in the distal promoter of DLL1. Conclusions. DLL1, which encodes Delta-like 1, the ligand for Notch3, is strongly implicated as the chromosome 6q27 VL susceptibility gene.

Insulin temporal sensitivity and its signaling pathway in the rat pineal gland

Aims: In our previous work, we reported that the insulin potentiating effect on melatonin synthesis is regulated by a post-transcriptional mechanism. However, the major proteins of the insulin signaling pathway (ISP) and the possible pathway component recruited on the potentiating effect of insulin had not been characterized. A second question raised was whether windows of sensitivity to insulin exist in the pineal gland due to insulin rhythmic secretion pattern. Main methods: Melatonin content from norepinephrine(NE)-synchronized pineal gland cultures was quantified by high performance liquid chromatography with electrochemical detection and arylalkylamine-N-acetyltransferase (AANAT) activity was assayed by radiometry. Immunoblotting and immunoprecipitation techniques were performed to establish the ISP proteins expression and the formation of 14-3-3: AANAT complex, respectively. Key findings: The temporal insulin susceptibility protocol revealed two periods of insulin potentiating effect, one at the beginning and another one at the end of the in vitro induced ""night"". In some Timed-insulin Stimulation (TSs), insulin also promoted a reduction on melatonin synthesis, showing its dual action in cultured pineal glands. The major ISP components, such as IR beta, IGF-1R, IRS-1, IRS-2 and PI3K(p85), as well tyrosine phosphorylation of pp85 were characterized within pineal glands. Insulin is not involved in the 14-3-3:AANAT complex formation. The blockage of PI3K by LY 294002 reduced melatonin synthesis and AANAT activity. Significance: The present study demonstrated windows of differential insulin sensitivity, a functional ISP and the PI3K-dependent insulin potentiating effect on NE-mediated melatonin synthesis, supporting the hypothesis of a crosstalk between noradrenergic and insulin pathways in the rat pineal gland. (C) 2010 Elsevier Inc. All rights reserved.

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.

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.

False-positive results of a rapid K39-based strip test and Chagas disease

Background: The definitive diagnosis of visceral. leishmaniasis (VL) requires invasive procedures with demonstration of amastigotes in tissue or promastigotes in culture. Unfortunately, these approaches require laboratory materials not available in poor countries where the disease is endemic. The correct diagnosis of VL is important, and made more difficult by the fact that several common tropical diseases such as malaria, disseminated tuberculosis, and enteric fever share the same clinical presentation. Serological tests have been developed to replace parasitological diagnosis in the field. A commercially available K39-based strip test for VL has been developed for this purpose. The endemic area of leishmaniasis in Brazil overlaps the endemic area of Chagas disease, a disease that can cause false-positive serological test results. The aim of this study was to evaluate the incidence of false-positive exams using a rapid test for VL in patients with Chagas disease. Methods: A rapid test based on the recombinant K39 antigen of Leishmania was used in: (1) 30 patients with confirmed Chagas disease, (2) 30 patients with a serological diagnosis of Chagas disease by ELISA, indirect immunofluorescence, indirect hemagglutination, and chemiluminescence, (3) 30 healthy patients from a non-endemic area as the control group, (4) 30 patients with confirmed VL, and (5) 20 patients with proved cutaneous leishmaniasis. Results: The sensitivity and specificity of the rapid strip test were 100% when compared with healthy volunteers and those with confirmed Chagas disease. One false-positive result occurred in the group with Chagas disease diagnosed by serological tests (specificity of 96%). Conclusion: The rapid test based on recombinant K39 is a useful diagnostic assay, and a false-positive result rarely occurs in patients with a serological diagnosis of Chagas disease. (C) 2008 International Society for Infectious Diseases. Published by Elsevier Ltd. 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

Neurose visceral: estudo de um distúrbio urbano

O enfoque fenomenológico de Alonso Fernandes foi a base deste estudo. O autor tenta provar que houve uma evolução qualitativa na forma de descarga da tensão excessiva, um desembocar somático da angústia. Melhor definindo, nos dias de hoje, não há mais lugar para a histeria demonstrativa, teatral, necessitando palco para bem resultar. A vida atual, impessoal, ativa e materialista tornou obsoleto o mecanismo transformador da angústia reprimida em símbolo corporal. O endeusamento do jovem, a falta de espaço, o nível de aspiração muito elevado e o estresse em alta doses torna compreensível que seja sobre este mesmo corpo que ele lance todo o excesso de tensão e angústia que é ensejado pela vida urbana. O presente estudo indaga a existência de uma patologia especifica para os indivíduos que reagem desta forma. Para tal verificação usou-se 3 grupos de 30 indivíduos subdivididos em: doentes de "fundo nervoso", doentes "orgânicos" e sadios. Dois tipos de instrumento foram aplicados com o objetivo de estudar o perfil de personalidade da amostra: O Inventário de Personalidade MHPI e um questionário que abrangesse o tipo de vida, costumes, hábitos, renda, escolaridade, etc do grupo em estudo. A hipótese básica é que não há uma patologia mental específica nos pacientes com doenças de "fundo nervoso" e que fatores tais como a exiguidade do espaço vital, o nível de aspiração, a preocupação com a autoimagem e o nível de estresse influenciam predominantemente a personalidade dos sujeitos pertencentes ao grupo das doenças psicossomáticas. Comprovou-se com boa margem de certeza a ideia de que a fuga para o corpo não é um quadro patológico delimitado mas sim um mecanismo de defesa, uma ajuda ao indivíduo obrigado a sobreviver as pressões de nossos dias. Além disto, a existência de respostas relativas a um nível de aspiração exagerado no grupo de doentes de "fundo nervoso" comprova ser tal variável uma das grandes vertentes propiciadoras da escolha da via somática como forma de descarga da angústia.