bluuebunny/crossref_metadata_2025 huggingface dataset:
Generation and characterization of transgenic mice expressing mitochondrial targeted red fluorescent protein selectively in neurons: modeling mitochondriopathy in excitotoxicity and amyotrophic lateral sclerosis
Authors: Wang Yi , Pan Yan , Price Ann , Martin Lee J
Published: November 2011

Background

Mitochondria have roles or appear to have roles in the pathogenesis of several chronic age-related and acute neurological disorders, including Charcot-Marie-Tooth disease, amyotrophic lateral sclerosis, Parkinson's disease, and cerebral ischemia, and could be critical targets for development of rational mechanism-based, disease-modifying therapeutics for treating these disorders effectively. A deeper understanding of neural tissue mitochondria pathobiologies as definitive mediators of neural injury, disease, and cell death merits further study, and the development of additional tools to study neural mitochondria will help achieve this unmet need.

Results

We created transgenic mice that express the coral (Discosoma sp.) red fluorescent protein DsRed2 specifically in mitochondria of neurons using a construct engineered with a Thy1 promoter, specific for neuron expression, to drive expression of a fusion protein of DsRed2 with a mitochondrial targeting sequence. The biochemical and histological characterization of these mice shows the expression of mitochondrial-targeted DsRed2 to be specific for mitochondria and concentrated in distinct CNS regions, including cerebral cortex, hippocampus, thalamus, brainstem, and spinal cord. Red fluorescent mitochondria were visualized in cerebral cortical and hippocampal pyramidal neurons, ventrobasal thalamic neurons, subthalamic neurons, and spinal motor neurons. For the purpose of proof of principle application, these mice were used in excitotoxicity paradigms and double transgenic mice were generated by crossing Thy1-mitoDsRed2 mice with transgenic mice expressing enhanced-GFP (eGFP) under the control of the Hlxb9 promoter that drives eGFP expression specifically in motor neurons and by crossing Thy1-mitoDsRed2 mice to amyotrophic lateral sclerosis (ALS) mice expressing human mutant superoxide dismutase-1.

Conclusions

These novel transgenic mice will be a useful tool for better understanding the biology of mitochondria in mouse and cellular models of human neurological disorders as exemplified by the mitochondrial swelling and fission seen in excitotoxicity and mouse ALS.
Red blood cell transfusion and increased length of storage are not associated with deep vein thrombosis in medical and surgical critically ill patients: a prospective observational cohort study
Authors: Katsios Christina , Griffith Lauren , Spinella Philip , Lacroix Jacques , Crowther Mark , Hebert Paul , Meade Maureen , Geerts William , Rabbat Christian , Cook Deborah
Published: November 2011

Introduction

With prolonged storage times, cell membranes of red blood cells (RBCs) undergo morphologic and biochemical changes, termed 'RBC storage lesions'. Storage lesions may promote inflammation and thrombophilia when transfused. In trauma patients, RBC transfusion was an independent risk factor for deep vein thrombosis (DVT), specifically when RBC units were stored > 21 days or when 5 or more units were transfused. The objective of this study was to determine if RBC transfusions or RBC storage age predicts incident DVT in medical or surgical intensive care unit (ICU) patients.

Methods

Using a database which prospectively enrolled 261 patients over the course of 1 year with an ICU stay of at least 3 days, we analyzed DVT and RBC transfusions using Cox proportional hazards regression. Transfusions were analyzed with 4 thresholds, and storage age using 3 thresholds. DVTs were identified by twice-weekly proximal leg ultrasounds. Multivariable analyses were adjusted for 4 significant DVT predictors in this population (venous thrombosis history, chronic dialysis, platelet transfusion and inotropes).

Results

Of 261 patients, 126 (48.3%) had at least 1 RBC transfusion; 46.8% of those transfused had ≥ 5 units in ICU. Patients receiving RBCs were older (68.8 vs 64.1 years), more likely to be female (47.0 vs 30.7), sicker (APACHEII 26.8 vs 24.4), and more likely to be surgical (21.4 vs 8.9) (P < 0.05). The total number of RBCs per patient was 1-64, mean was 6.3 (SD 7.5), median was 4 (IQR 2,8). In univariate analyses, there was no association between DVT and RBC exposure (1 day earlier, 3 days earlier, 7 days earlier, or ever) or RBC storage (≤ 7 or > 7 days, ≤ 14 or > 14 days, ≤ 21 or > 21 days). Among patients transfused, no multivariable analyses showed that RBC transfusion or storage age predicted DVT. Trends were counter to the hypothesis (e.g., RBC storage for ≤ 7 days suggested a higher DVT risk compared to > 7 days (HR 5.3; 95% CI 1.3-22.1).

Conclusions

We were unable to detect any association between RBC transfusions or prolonged red cell storage and increased risk of DVT in medical or surgical ICU patients. Alternate explanations include a lack of sufficient events or patients' interaction, between patient groups, a mixing of red cell storage times creating differential effects on DVT risk, and unmeasured confounders.
Inherent Growth Hormone Resistance in the Skeletal Muscle of the Fine Flounder Is Modulated by Nutritional Status and Is Characterized by High Contents of Truncated GHR, Impairment in the JAK2/STAT5 Signaling Pathway, and Low IGF-I Expression
Authors: Fuentes Eduardo N. , Einarsdottir Ingibjörg Eir , Valdes Juan Antonio , Alvarez Marco , Molina Alfredo , Björnsson Björn Thrandur
Published: October 2011

A detailed understanding of how the GH and IGF-I regulate muscle growth, especially in early vertebrates, is still lacking. The fine flounder is a flatfish species exhibiting remarkably slow growth, representing an intriguing model for elucidating growth regulatory mechanisms. Key components of the GH system were examined in groups of fish during periods of feeding, fasting, and refeeding. Under feeding conditions, there is an inherent systemic and local (muscle) GH resistance, characterized by higher levels of plasma GH than of IGF-I, skeletal muscle with a greater content of the truncated GH receptor (GHRt) than of full-length GHR (GHRfl), an impaired activation of the Janus kinase 2 (JAK2)-signal transducers and activators of transcription 5 (STAT5) signaling pathway, and low IGF-I expression. Fasting leads to further elevation of plasma GH levels concomitant with suppressed IGF-I levels. The ratio of GHRfl to GHRt in muscle decreases during fasting, causing an inactivation of the JAK2/STAT5 signaling pathway and suppressed IGF-I expression, further impairing growth. When fish are returned to nutritionally favorable conditions, plasma GH levels decrease, and the ratio of GHRfl to GHRt in muscle increases, triggering JAK2/STAT5 reactivation and local IGF-I expression, concomitant with increased growth. The study suggests that systemic IGF-I is supporting basal slow growth in this species, without ruling out that local IGF-I is participating in muscle growth. These results reveal for the first time a unique model of inherent GH resistance in the skeletal muscle of a nonmammalian species and contribute to novel insights of the endocrine and molecular basis of growth regulation in earlier vertebrates.
Ultrastructural study of transcription factories in mouse erythroblasts
Authors: Eskiw Christopher H. , Fraser Peter
Published: November 2011

RNA polymerase II (RNAPII) transcription has been proposed to occur at transcription factories; nuclear focal accumulations of the active, phosphorylated forms of RNAPII. The low ratio of transcription factories to active genes and transcription units suggests that genes must share factories. Our previous analyses using light microscopy have indicated that multiple genes could share the same factory. Furthermore, we found that a small number of specialized transcription factories containing high levels of the erythroid-specific transcription factor KLF1 preferentially transcribed a network of KLF1-regulated genes. Here we used correlative light microscopy in combination with energy filtering transmission electron microscopy (EFTEM) and electron microscopy in situ hybridization (EMISH) to analyse transcription factories, transcribing genes, and their nuclear environments at the ultrastructural level in ex vivo mouse foetal liver erythroblasts. We show that transcription factories in this tissue can be recognized as large nitrogen-rich structures with a mean diameter of 130 nm, which is considerably larger than that previously seen in transformed cultured cell lines. We show that KLF1-specialized factories are significantly larger, with the majority of measured factories occupying the upper 25th percentile of this distribution with an average diameter of 174 nm. In addition, we show that very highly transcribed genes associated with erythroid differentiation tend to occupy and share the largest factories with an average diameter of 198 nm. Our results suggest that individual factories are dynamically organized and able to respond to the increased transcriptional load imposed by multiple highly transcribed genes by significantly increasing in size.
Regulation of brain temperature in winter-acclimatized reindeer under heat stress
Authors: Blix Arnoldus Schytte , Walløe Lars , Folkow Lars P.
Published: October 2011

Reindeer (Rangifer tarandus) are protected against the Arctic winter cold by thick fur of prime insulating capacity and hence have few avenues of heat loss during work. We have investigated how these animals regulate brain temperature under heavy heat loads. Animals were instrumented for measurements of blood flow, tissue temperatures and respiratory frequency (f) under full anaesthesia, whereas measurements were also made in fully conscious animals while in a climatic chamber or running on a treadmill. At rest, brain temperature (Tbrain) rose from 38.5±0.1°C at 10°C to 39.5±0.2°C at 50°C, while f increased from ×7 to ×250 breaths min–1, with a change to open-mouth panting (OMP) at Tbrain 39.0±0.1°C, and carotid and sublingual arterial flows increased by 160% and 500%, respectively. OMP caused jugular venous and carotid arterial temperatures to drop, presumably owing to a much increased respiratory evaporative heat loss. Angular oculi vein (AOV) flow was negligible until Tbrain reached 38.9±0.1°C, but it increased to 0.81 ml min–1 kg–1 at Tbrain 39.2±0.2°C. Bilateral occlusion of both AOVs induced OMP and a rise in Tbrain and f at Tbrain >38.8°C. We propose that reindeer regulate body and, particularly, brain temperature under heavy heat loads by a combination of panting, at first through the nose, but later, when the heat load and the minute volume requirements increase due to exercise, primarily through the mouth and that they eventually resort to selective brain cooling.
Relationship between oxidizable fatty acid content and level of antioxidant glutathione peroxidases in marine fish
Authors: Grim Jeffrey M. , Hyndman Kelly A. , Kriska Tamas , Girotti Albert W. , Crockett Elizabeth L.
Published: October 2011

Biological membranes can be protected from lipid peroxidation by antioxidant enzymes including catalase (CAT) and selenium-dependent glutathione peroxidases 1 and 4 (GPx1 and GPx4). Unlike GPx1, GPx4 can directly detoxify lipid hydroperoxides in membranes without prior action of phospholipase A2. We hypothesized that (1) GPx4 is enhanced in species that contain elevated levels of highly oxidizable polyunsaturated fatty acids (PUFA) and (2) activities of antioxidant enzymes are prioritized to meet species-specific oxidative stresses. In this study we examined (i) activities of the oxidative enzyme citrate synthase (CS) and antioxidant (CAT, GPx1 and GPx4) enzymes, (ii) GPx4 protein expression, and (iii) phospholipid composition in livers of five species of marine fish (Myxine glutinosa, Petromyzon marinus, Squalus acanthias, Fundulus heteroclitus and Myoxocephalus octodecemspinosus) that contain a range of PUFA. GPx4 activity was, on average, 5.8 times higher in F. heteroclitus and S. acanthias than in the other three marine fish species sampled. Similarly, activities of CAT and GPx1 were highest in S. acanthias and F. heteroclitus, respectively. GPx4 activity for all species correlates with membrane unsaturation, as well as oxidative activity as indicated by CS. These data support our hypothesis that GPx4 level in marine fish is a function, at least in part, of high PUFA content in these animals. GPx1 activity was also correlated with membrane unsaturation, indicating that marine species partition resources among glutathione-dependent defenses for protection from the initial oxidative insult (e.g. H2O2) and to repair damaged lipids within biological membranes.
Ammonotely in a neotropical frugivorous bat as energy intake decreases
Authors: Herrera M. L. Gerardo , Osorio M. Jazmín , Mancina G. Carlos A.
Published: October 2011

We tested the role of increased ammonia in urine as an energy- and/or nitrogen (N)-saving mechanism in the great fruit-eating bat Artibeus lituratus (Phyllostomidae). We compared N excretion in two groups of bats fed energy-rich (2.75 kJ g–1 wet mass) or energy-poor diets (0.7 kJ g–1 wet mass). Within each diet, bats were assigned to different N contents. In order to function as an energy-saving mechanism, ammonia production should increase with decreasing energy intake. To function as an N-saving mechanism, ammonia production should increase with decreasing N intake. Because we varied both diet energy density and N content, our study design allowed us to test these two possibilities simultaneously. Bats had higher food intake rate and, consequently, higher N intake rate on the energy-poor diet, but energy intake rate was lower. Most bats on the energy-rich diet were ureotelic whereas on the energy-poor diet bats were ureotelic, ammonotelic or ureo-ammonotelic. Bats fed the energy-poor diet had a higher excretion rate of ammonia and a higher percent of N excreted as ammonia. Percent N ammonia and ammonia excretion rate were inversely related to energy intake, but they were not related to N intake. By favoring ammonia production over urea, bats on the energy-poor diet may save up to 1% of their basal metabolic rate. Consumption of energy-dilute fruits by fruit bats might affect the way in which N wastes are excreted, favoring the excretion of ammonia N when food intake is accompanied by the ingestion of large volumes of water.
Origins of Western diseases
Authors: Quinn MJ
Published: November 2011

Recent gynaecological studies show that childbirth, constipation, trauma and surgery cause injuries to autonomic nerves at different anatomical sites in the female pelvis resulting in endometriosis, adenomyosis and fibroids. Re-growth of abnormal nerves causes allodynic symptoms (‘light touch causing pain or discomfort’) some years later including vulvodynia, dyspareunia, dysmenorrhea, irritative bladder and bowel symptoms. Further consequences of autonomic denervation include tissue hypoplasia and hyperplasia, visceral dysfunction, susceptibility to infection, alcohol, tobacco and drugs, as well as pain with sensitization of the central nervous system. The ‘autonomic denervation’ view extrapolates these observations from the female pelvis to the varied anatomy of branches of the cardiac and coeliac plexi to provide primary mechanisms for many forms of Western disease. This account sets out the autonomic denervation view, identifies features of autonomic denervation in extrapelvic organs, and, contrasts it with prior accounts of chronic Western diseases including those of DP Burkitt, PRJ Burch and DP Barker.
Schizophrenia as segmental progeria
Authors: Papanastasiou Evangelos , Gaughran Fiona , Smith Shubulade
Published: November 2011

Schizophrenia is associated with a variety of physical manifestations (i.e. metabolic, neurological) and despite psychotropic medication being blamed for some of these (in particular obesity and diabetes), there is evidence that schizophrenia itself confers an increased risk of physical disease and early death. The observation that schizophrenia and progeroid syndromes share common clinical features and molecular profiles gives rise to the hypothesis that schizophrenia could be conceptualized as a whole body disorder, namely a segmental progeria. Mammalian cells employ the mechanisms of cellular senescence and apoptosis (programmed cell death) as a means to control inevitable DNA damage and cancer. Exacerbation of those processes is associated with accelerated ageing and schizophrenia and this warrants further investigation into possible underlying biological mechanisms, such as epigenetic control of the genome.
Kimberly-Clark Latin America Builds an Optimization-Based System for Machine Scheduling
Authors: Shaikh Nazrul , Prabhu Vittal , Abril Danilo , Sánchez David , Arias Jorge , Rodríguez Esteban , Riaño Germán
Published: October 2011

During a single planning period, Kimberly-Clark Latin America manufactures dozens of stock-keeping units (SKUs) in varying quantities using a few machines. The same SKU can be manufactured on multiple machines, some of which are more efficient than others. In addition, the setup time for an SKU is sequence dependent, and its demand is stochastic between planning periods. The stochastic demand necessitates changing production plans each planning period; given the large number of SKUs and small number of machines, this leads to inefficiencies. This paper describes the formulation and corresponding solution approach of an integrated inventory, production-planning, and detailed scheduling model to address the inefficiencies in lot sizing, production scheduling, and inventory management. The paper's key contribution is the solution approach, which solves the resultant industry-size NP-hard problem in minutes. The solution quality and its implementation have been tested extensively, and the model has been successfully deployed in five countries. A reduction in finished product inventories of up to 45 percent, an increase in yield and uptime of 2 percent, and improvements in service levels of 2.4 percent are directly attributable to the model and the solution approach highlighted in the paper.
An Improved Model for the Rate–Level Functions of Auditory-Nerve Fibers
Authors: Heil Peter , Neubauer Heinrich , Irvine Dexter R. F.
Published: October 2011

Acoustic information is conveyed to the brain by the spike patterns in auditory-nerve fibers (ANFs). In mammals, each ANF is excited via a single ribbon synapse in a single inner hair cell (IHC), and the spike patterns therefore also provide valuable information about those intriguing synapses. Here we reexamine and model a key property of ANFs, the dependence of their spike rates on the sound pressure level of acoustic stimuli (rate–level functions). We build upon the seminal model of Sachs and Abbas (1974), which provides good fits to experimental data but has limited utility for defining physiological mechanisms. We present an improved, physiologically plausible model according to which the spike rate follows a Hill equation and spontaneous activity and its experimentally observed tight correlation with ANF sensitivity are emergent properties. We apply it to 156 cat ANF rate–level functions using frequencies where the mechanics are linear and find that a single Hill coefficient of 3 can account for the population of functions. We also demonstrate a tight correspondence between ANF rate–level functions and the Ca2+dependence of exocytosis from IHCs, and derive estimates of the effective intracellular Ca2+concentrations at the individual active zones of IHCs. We argue that the Hill coefficient might reflect the intrinsic, biochemical Ca2+cooperativity of the Ca2+sensor involved in exocytosis from the IHC. The model also links ANF properties with properties of psychophysical absolute thresholds.
A Shh/miR-206/BDNF Cascade Coordinates Innervation and Formation of Airway Smooth Muscle
Authors: Radzikinas Kelsi , Aven Linh , Jiang Zhihua , Tran Thanh , Paez-Cortez Jesus , Boppidi Karthik , Lu Jining , Fine Alan , Ai Xingbin
Published: October 2011

Dysfunctional neural control of airway smooth muscle (ASM) is involved in inflammatory diseases, such as asthma. However, neurogenesis in the lung is poorly understood. This study uses mouse models to investigate developmental mechanisms of ASM innervation, a process that is highly coordinated with ASM formation during lung branching morphogenesis. We show that brain-derived neurotrophic factor (BDNF) is an essential ASM-derived signal for innervation. Although BDNF mRNA expression is temporally dissociated with ASM formation and innervation, BDNF protein is coordinately produced through post-transcriptional suppression by miR-206. Using a combination of chemical and genetic approaches to modulate sonic hedgehog (Shh) signaling, a pathway essential for lung branching and ASM formation, we show that Shh signaling blocks miR-206 expression, which in turn increases BDNF protein expression. Together, our work uncovers a functional cascade that involves Shh, miR-206 and BDNF to coordinate ASM formation and innervation.
The Hippocampus Supports Both Recollection and Familiarity When Memories Are Strong
Authors: Smith Christine N. , Wixted John T. , Squire Larry R.
Published: November 2011

Recognition memory is thought to consist of two component processes—recollection and familiarity. It has been suggested that the hippocampus supports recollection, while adjacent cortex supports familiarity. However, the qualitative experiences of recollection and familiarity are typically confounded with a quantitative difference in memory strength (recollection > familiarity). Thus, the question remains whether the hippocampus might in fact support familiarity-based memories whenever they are as strong as recollection-based memories. We addressed this problem in a novel way by using the Remember/Know procedure, which allowed us to explicitly match the confidence and accuracy of Remember and Know decisions. As in earlier studies, recollected items had higher accuracy and confidence than familiar items, and hippocampal activity was higher for recollected items than for familiar items. Furthermore, hippocampal activity was similar for familiar items, misses, and correct rejections. When the accuracy and confidence of recollected and familiar items were matched, the findings were dramatically different. Hippocampal activity was now similar for recollected and familiar items. Importantly, hippocampal activity was also greater for familiar items than for misses or correct rejections (as well as for recollected items vs misses or correct rejections). Our findings suggest that the hippocampus supports both recollection and familiarity when memories are strong.
Highly Specific Role of Hypocretin (Orexin) Neurons: Differential Activation as a Function of Diurnal Phase, Operant Reinforcement versus Operant Avoidance and Light Level
Authors: McGregor Ronald , Wu Ming-Fung , Barber Grace , Ramanathan Lalini , Siegel Jerome M.
Published: October 2011

Hypocretin (Hcrt) cell loss is responsible for narcolepsy, but Hcrt's role in normal behavior is unclear. We found that Hcrt knock-out mice were unable to work for food or water reward during the light phase. However, they were unimpaired relative to wild-type (WT) mice when working for reward during the dark phase or when working to avoid shock in the light or dark phase. In WT mice, expression of Fos in Hcrt neurons occurs only in the light phase when working for positive reinforcement. Expression was seen throughout the mediolateral extent of the Hcrt field. Fos was not expressed when expected or unexpected unearned rewards were presented, when working to avoid negative reinforcement, or when given or expecting shock, even though these conditions elicit maximal electroencephalogram (EEG) arousal. Fos was not expressed in the light phase when light was removed. This may explain the lack of light-induced arousal in narcoleptics and its presence in normal individuals. This is the first demonstration of such specificity of arousal system function and has implications for understanding the motivational and circadian consequences of arousal system dysfunction. The current results also indicate that comparable and complementary specificities must exist in other arousal systems.
Athen – Eine wehrhafte Demokratie? Überlegungen zum Stasisgesetz Solons und zum Ostrakismos
Authors: Schmitz Winfried
Published: October 2011

Zu den politischen Reformen Solons gehört das Stasisgesetz, das in der Forschung unterschiedlich gedeutet wird, meist als Versuch Solons, einen Bürgerkrieg im Keim zu ersticken, weil opponierende Adelige damit rechnen mußten, daß sich ihnen die Mehrheit der attischen Bürger entgegenstellte. Eine Untersuchung der frühen Belege für stásis zeigt, daß das Wort den Bürgerkrieg bezeichnen kann, häufig aber einen Konflikt meint, eine Spaltung der Bürgerschaft in einer politisch brisanten Situation, die durch eine Abstimmung entschieden wurde, so daß eine gewaltsame Auseinandersetzung vermieden werden konnte. In einen solchen Kontext gestellt ist das Stasisgesetz kein Aufruf an die Bürger, bei einem Bürgerkrieg zu den Waffen zu greifen, sondern kann als Verpflichtung gedeutet werden, in einer politisch brisanten Situation an einer Abstimmung teilzunehmen. Der Kontext, in dem das Gesetz überliefert ist, legt nahe, daß sich das Gesetz auf Anklagen vor dem Areopag bezieht. Bei einem Tyrannisversuch, einem Kampf um die Ämter oder einem scharfen politischen Konflikt wurden also die Areopagiten verpflichtet, bei der Abstimmung durch Stimmabgabe Stellung für die eine oder andere Seite zu beziehen. Das Stasisgesetz kann daher als geringer formalisierte Vorform des Ostrakismos verstanden werden. Möglicherweise weil sich das Entscheidungsverfahren im Areopag nicht bewährt hatte, übertrug Kleisthenes die Entscheidung am Ende des 6. Jh. vom Areopag auf das Volk und ersetzte die Verpflichtung zur Stimmabgabe durch ein Mindestquorum.
An Inquiry-Based Field & Laboratory Investigation of Leaf Decay: A Critical Aquatic Ecosystem Function
Authors: Hopkins Jessica M. , Smith Rosemary J.
Published: October 2011

Effective investigations incorporate all four features of constructivist teaching. This high school or college-level field investigation guides teachers (and students) through the stages of inquiry. The focal concept is ecosystem function, specifically leaf decay rates in aquatic environments. Teachers elicit their students' prior knowledge and use it to generate discussion on variables that influence decay rates. Students engage in designing and conducting experiments. The learning cycle is continued when students apply their new knowledge and receive feedback, and completed when students return to their initial conceptions of leaf decay and reflect on the knowledge they gained through scientific experimentation.
Expression and uptake of the thyroxine-binding protein transthyretin is regulated by oxygen in primary trophoblast placental cells
Authors: Patel J , Landers K A , Mortimer R H , Richard K
Published: November 2011

Transplacental delivery of maternal thyroid hormones to the fetus, in particular thyroxine (T4), is critical in ensuring normal fetal neurological development. The fetus relies on maternal T4till around 16 weeks gestation, but mechanisms of placental T4transport are not yet fully elucidated. Placenta produces, secretes and takes up the thyroid hormone-binding protein transthyretin (TTR). Many placental genes are regulated by oxygen levels, which are relatively low (1%) in the early first trimester, rising to 3% in the mid first trimester and 8% in the early second trimester and thereafter. We examined the expression and uptake of TTR in isolated primary human placental cytotrophoblast cells cultured under different oxygen concentrations (1, 3, 8, 21% O2and 200 μM desferrioxamine (DFO)) for 24 h. We observed sevenfold higher expression ofTTRmRNA and protein levels at 1% O2than at 8 and 21% O2. Significant increases were observed after culture at 3% O2and following DFO treatment. We observed significantly higher uptake of125I-TTR and Alexa-594-TTR when cells were cultured at 1 and 3% O2and in the presence of 200 μM DFO than at 8 and 21% O2. When JEG-3 choriocarcinoma cells were transfected with TTR promoter reporter constructs, increased luciferase activity was measured in cells cultured at 1 and 3% O2in comparison to 8 and 21% O2. We conclude that placental TTR expression and uptake is increased by the relative hypoxia observed in the first trimester of pregnancy, a time when materno–fetal T4transfer is the sole source of fetal T4.
The emerging role of C/EBPs in glucocorticoid signaling: lessons from the lung
Authors: Roos Abraham B , Nord Magnus
Published: November 2011

Glucocorticoids (GCs) have been successfully used in the treatment of inflammatory diseases for decades. However, there is a relative GC resistance in several inflammatory lung disorders, such as chronic obstructive pulmonary disease (COPD), but still the mechanism(s) behind this unresponsiveness remains unknown. Interaction between transcription factors and the GC receptor contribute to GC effects but may also provide mechanisms explaining steroid resistance. CCAAT/enhancer-binding protein (C/EBP) transcription factors are important regulators of pulmonary gene expression and have been implicated in inflammatory lung diseases such as asthma, pulmonary fibrosis, cystic fibrosis, sarcoidosis, and COPD. In addition, several studies have indicated a role for C/EBPs in mediating GC effects. In this review, we discuss the different mechanisms of GC action as well as the function of the lung-enriched members of the C/EBP transcription factor family. We also summarize the current knowledge of the role of C/EBP transcription factors in mediating the effects of GCs, with emphasis on pulmonary effects, and their potential role in mediating GC resistance.
Hepatitis B and C virus infection among Brazilian Amazon riparians
Authors: Oliveira Claudia Suellen Ferro de , Silva Adenielson Vilar e , Santos Kemper Nunes dos , Fecury Amanda Alves , Almeida Marcella Kelly Costa de , Fernandes Adriana Prado , Costa Carlos Araújo da , Freitas Andrei Silva , Corvelo Tereza Cristina de Oliveira , Martins Luisa Caricio
Published: October 2011

INTRODUCTION: Viral hepatitis is a major public health concern in Brazil. There are few past studies on this issue, especially among riparian communities. This study aims at determining the seroprevalence of viral hepatitis B and C in the riparian community of Pacuí Island, within the Cametá municipality of Pará State, Brazil. Moreover, this study aims to investigate the principal risk factors that this community is exposed to. METHODS: The current study has accessed blood samples from 181 volunteers who have answered an epidemiological questionnaire. Analyses on serological markers have been tested with commercial ELISA kits for detecting HBsAg, total anti-HBc, anti-HBs, and anti-HCV. Within seroreactive patients for HCV, RT-PCR and line probe assay have been performed to identify the viral genotype. RESULTS: In the serological marker analysis for hepatitis B, no reactivity for HBsAg, rate of 1.1% for total anti-HBc, and rate of 19.3% for anti-HBs have been observed. On hepatitis C, 8.8% seroprevalence has been found, in which 62.5% have gotten viral RNA. Among the risk factors studied, the following have been highlighted: non-use of condoms, sharing of cutting instruments, use of illicit drugs, and reports of family disease with HBV or HCV. CONCLUSIONS: The vaccination coverage against HBV is low, and the high prevalence of HCV within this community has been observed.
Avaliação de parâmetros morfométricos calculados a partir do contorno de lesões de mama em ultrassonografias na distinção das categorias do sistema BI-RADS
Authors: Calas Maria Julia Gregorio , Alvarenga André Victor , Gutfilen Bianca , Pereira Wagner Coelho de Albuquerque
Published: November 2011

OBJETIVO: Avaliar o desempenho de parâmetros morfométricos, calculados a partir do contorno de lesões de mama em ultrassonografias, na quantificação de suas características morfológicas e na distinção das categorias 2, 3, 4 e 5 do sistema de classificação ecográfica BI-RADS. MATERIAIS E MÉTODOS: A casuística é composta por 40 casos com registro ortogonal de pacientes submetidas à cirurgia. A partir das lesões segmentadas, foram calculados cinco parâmetros morfométricos para quantificar o contorno e a forma das lesões: razão de área, razão de superposição, valor residual normalizado, circularidade e razão entre largura e profundidade. A análise discriminante linear foi usada para selecionar os parâmetros mais significativos na distinção das características morfológicas das lesões, usando como figura de mérito a curva ROC. RESULTADOS: A razão de superposição foi capaz de diferenciar estatisticamente as lesões classificadas como BI-RADS 3 daquelas classificadas como BI-RADS 4 (a = 5%; p = 0,015), sendo, também, o parâmetro morfométrico que apresentou melhor desempenho na diferenciação entre lesões malignas e benignas. CONCLUSÃO: Este resultado indica que a análise morfométrica de lesões de mama em ultrassonografias tem potencial para auxiliar na distinção de pacientes que deveriam ser submetidas à biópsia, daquelas que poderiam manter controle por métodos de imagem.
Biópsia transtorácica de nódulos e massas pulmonares dirigida por tomografia computadorizada
Authors: Chojniak Rubens , Pinto Paula Nicole Vieira , Ting Chiang Jeng , Cohen Marcela Pecorah , Guimarães Marcos Duarte , Yu Liao Shin , Bitencourt Almir Galvão Vieira
Published: November 2011

Biópsia percutânea dirigida por tomografia computadorizada tem sido amplamente utilizada como um procedimento efetivo e seguro para obtenção de diagnóstico histológico em muitas situações clínicas e em diversos órgãos. No pulmão, a biópsia percutânea tornou-se uma das principais escolhas para investigação de nódulos e massas. Sua versatilidade permite o acesso de lesões nas diversas localizações do pulmão, podendo ser utilizada para lesões periféricas e profundas mesmo de pequenas dimensões. Discutiremos as indicações, os aspectos técnicos do procedimento e os índices esperados de sucesso e complicação das biópsias percutâneas de nódulos e massas pulmonares.
Doença de Gorham da escápula e clavícula: relato de caso e evolução de dois anos de uma afecção rara
Authors: Oliveira Paulo Cesar Rocha , Alcantara Fabio Peixoto , Judice Paola Lima Pasini , Batista Giovani Rodrigues , Teles Ilailson de Goes , Antunes Julio Salgado
Published: November 2011

A doença de Gorham é uma rara desordem osteolítica, de etiologia controversa, que pode afetar qualquer osso. O substrato histopatológico é a substituição óssea por uma formação expansiva de natureza vascular agressiva, não neoplásica. Descrevemos os achados radiográficos, tomográficos e de ressonância magnética de um caso desta afecção acometendo a escápula esquerda e, dois anos depois, a clavícula ipsilateral.
Changes in the volume and histology of endometriosis foci in rats treated with copaiba oil (Copaiferalangsdorffii)
Authors: Nogueira Neto João , Lindoso Márcio Jorge de Souza , Coelho Laura Fernandes , Carvalho Rafael Antonio Freire , Rodrigues Taciana Gabrielle Pinheiro de Moura , Araújo Ana Gisélia Portela de , Girão Manuel João Batista Castelo , Schor Eduardo
Published: October 2011

PURPOSE: The aim of this study was to analyze the changes that occur in rats with experimental endometriosis after treatment with copaiba oil. METHODS: Experimental endometriosis was induced in rats. The experimental group received copaiba oil (Copaiferalangsdorffii) orally (0.63 mg/day), and the control group received a 0.9% sodium chloride solution orally (1 ml/100 g of body weight/day). Both groups were treated with gavage for 14 days. After this period, the animals were euthanized, and the implant volume was calculated. The autologous transplants were removed, dyed with hematoxylin-eosin, and analyzed by light microscopy. RESULTS: The average final volumes were significantly different between the groups (p=0.007). There was a significant increase (p=0.012) between the initial and final volumes in the control group, whereas treatment with Copaiferalangsdorffii caused a marked reduction in endometrial growth over time (p=0.016). Histologically, 6/11 (55.00%) rats in the experimental group had a well-preserved epithelial layer, and 3 (45.00%) had mildly preserved epithelium. The control group had seven cases (58.30%) of well-preserved epithelial cells and five cases (41.70%) of mildly preserved epithelial cells (p>0.05). CONCLUSION: Copaiba oil (Copaiferalangsdorffii) appears to be a promising alternative treatment for endometriosis.
Effects of albumin administration in serum liver enzymes of rats in the presence of extrahepatic biliary obstruction
Authors: Lessa Jorge Fernando Rebouças , Rangel Leonardo Siqueira , Costa Junior Nilton José de Almeida , Silva Orlando Castro e , Cruz Carlos Augusto Teixeira da , Sousa João Batista de
Published: October 2011

PURPOSE: To study the influence of albumin on changes of liver function in the extrahepatic biliary obstruction through an experimental model in rats. METHODS: Sixty rats were divided into four groups: Group C (Control): 6 animals. Group M (Fictitious Operation): 18 rats underwent laparotomy and handling of the bile ducts; Groups O (extrahepatic biliary obstruction) and A (Treated with 2% albumin): 18 animals in each group underwent ligation of the ductus liver; The animals in groups M, O and A were divided into three subgroups of 6 animals each to be killed in the 7, 14 and 21 days postoperative (POD). Blood was drawn for determination of total bilirubin (TB), indirect bilirubin (IB), direct bilirubin (DB), alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT). RESULTS: On POD 7, BI levels were 4.5 mg / dl in group O and 2.1 mg / dl in group A (p = 0.025). On the 14th POD, the levels of PA were 1185.2 U / l in the group and O 458.3 U / l in group A (p = 0.004). ALT levels were 101.7 U / l in the group O and 75.7 U / l in group A (= 0.037). On POD 21, the levels of ALP were 1069.5 U / l in the group O and 468.3 U / l in group A (p = 0, 004). CONCLUSION: The administration of albumin reduced the serum levels of bilirubin in the 7th day of supplementation
Fatores associados ao abandono do tratamento da tuberculose: uma revisão integrativa
Authors: Chirinos Narda Estela Calsin , Meirelles Betina Hörner Schlindwein
Published: October 2011

Revisão integrativa de literatura, em publicações científicas de 2000 a 2009, que objetivou evidenciar conceitos e fatores associados ao abandono do tratamento da tuberculose. Os dados foram coletados do portal da Biblioteca Virtual em Saúde/LILACS e da SciELO, utilizando os descritores: pacientes desistentes do tratamento, recusa do paciente ao tratamento, cooperação do paciente e adesão à medicação, em cruzamento com o descritor tuberculose. A busca originou 219 artigos, que, observados critérios de inclusão e exclusão, resultou em nove artigos completos. A análise dos dados formou as categorias Conceituando abandono de tratamento da tuberculose e Fatores associados ao abandono de tratamento da tuberculose. Considerou-se abandono ao tratamento da tuberculose a interrupção do uso de medicação por 30 dias ou mais. Os fatores associados relevantes foram: sociodemográficos, doenças associadas e assistência em saúde. A equipe de enfermagem/saúde deve focar abordagens de cuidado mais interativas e humanizadas, direcionadas a incrementar a adesão do paciente ao tratamento.
Do Fundef ao Fundeb: avaliando o passado para pensar o futuro: um estudo de caso no município de Pirapozinho-SP
Authors: Ramos Regina Celia , Di Giorgi Cristiano Amaral
Published: October 2011

Este artigo, que envolve a combinação de procedimentos quantitativos e qualitativos, traz resultados de pesquisa que analisou o impacto do Fundef na estruturação da rede municipal de ensino de Pirapozinho-SP, e mostra como estes resultados trazem subsídios para um funcionamento mais adequado da atual política de financiamento da educação. Constatou-se que, mesmo sem aumentar os recursos financeiros do ensino fundamental, o Fundef racionalizou e tornou mais eficiente a sua aplicação, diminuindo desvios e desperdícios, e que a instituição dos Conselhos de Acompanhamento e Controle Social possibilitou maior participação popular na fiscalização do executivo aumentando a transparência dos gastos com educação, que a constituição do Fundef abriu a possibilidade de implantação do Fundeb atualmente em vigor e que a melhoria no funcionamento deste está relacionada ao aumento da participação da sociedade nas decisões da política educacional e ao investimento na qualificação desta participação.
Qualitative environmental health research: an analysis of the literature, 1991-2008
Authors: Scammell Madeleine Kangsen
Published: October 2011

Qualitative research uses nonnumeric data to understand people's opinions, motives, understanding, and beliefs about events or phenomena. In this analysis, I report the use of qualitative methods and data in the study of the relationship between environmental exposures and human health. A primary search for peer-reviewed journal articles dated from 1991 through 2008 included the following three terms: qualitative, environ*, and health. Searches resulted in 3,155 records. Data were extracted and findings of articles analyzed to determine where and by whom qualitative environmental health research is conducted and published, the types of methods and analyses used in qualitative studies of environmental health, and the types of information qualitative data contribute to environmental health. The results highlight a diversity of disciplines and techniques among researchers who used qualitative methods to study environmental health. Nearly all of the studies identified increased scientific understanding of lay perceptions of environmental health exposures. This analysis demonstrates the potential of qualitative data to improve understanding of complex exposure pathways, including the influence of social factors on environmental health, and health outcomes.
Características de mastigação e deglutição na doença de Alzheimer
Authors: Tavares Thaíza Estrela , Carvalho Cecília Maria Resende Gonçalves de
Published: November 2011

OBJETIVOS: comparar as características de mastigação e deglutição em idosos com e sem Doença de Alzheimer (DA). MÉTODO: estudo comparativo desenvolvido com 86 idosos, na faixa etária entre 60 e 93 anos, de ambos os sexos, distribuídos nos grupos controle (sem DA, n=43) e experimental (com DA, n=43). A função cognitiva e o estadiamento da DA foram avaliados por meio da aplicação da CDR (Clinical Dementia Rating). Para a caracterização da mastigação e deglutição foi aplicado o protocolo de avaliação miofuncional orofacial. RESULTADOS: as características de mastigação e deglutição sofreram variações importantes quando comparados os dois grupos. Houve diferença significante para movimentos mandibulares, reflexo de deglutição, deglutições múltiplas, presença de resíduos e dificuldade para ingerir comprimidos. CONCLUSÕES: as características de mastigação e deglutição, de maneira geral, sofrem maior comprometimento nos idosos com DA, quando comparados a idosos saudáveis.
Crioplastia para tratamento da doença arterial fêmoro-poplítea
Authors: Lourenço Marco Antonio , Handa Gustavo Ioshio
Published: November 2011

CONTEXTO: O tratamento endovascular da doença arterial obstrutiva periférica apresenta baixa morbidade e mortalidade, no entanto, a perviedade dos stents a médio e longo prazo ainda é controversa. A crioplastia foi desenvolvida para reduzir os grandes desafios da angioplastia: dissecção, retração e reestenose. OBJETIVO: Avaliar os resultados clínicos e a perviedade a médio prazo em pacientes submetidos à técnica de crioplastia da doença arterial do território femoro-poplíteo. MÉTODOS: Pacientes com indicação de revascularização de membro inferior por técnica endovascular do território femoro-poplíteo, segundo as classificações clínicas de Fontaine e Rutherford e classificações anatômicas do TASC II, foram submetidos à crioplastia com cateter balão PolarCath®. No seguimento, foram avaliadas as manifestações clínicas e perviedade anatômica pelo duplex scan. RESULTADOS: Dez pacientes foram submetidos à angioplastia do território femoro-poplíteo utilizando a técnica de crioplastia. Nove pacientes apresentavam quadro clínico de claudicação limitante do membro inferior e um paciente apresentava úlcera isquêmica, três pacientes apresentavam lesão classe B pelo TASC II e sete pacientes, classe A. Sucesso técnico angiográfico inicial foi obtido em todos os casos, sendo que um caso necessitou do implante de stent devido à dissecção. Seguimento foi realizado em 9 pacientes, por período médio de 31,6 meses (28-35), com perviedade primária de 77,7% e perviedade secundária de 100%. Todos os pacientes apresentam-se assintomáticos no final do seguimento (Fontaine I). CONCLUSÕES: A crioplastia do território femoro-poplíteo é um método seguro, de baixa morbidade, com resultados a curto e médio prazo comparáveis à angioplastia convencional e com potencial de reduzir as taxas de dissecção e retração durante o procedimento, e redução do grau de reestenose a médio e longo prazo.
Quantidades médias no movimento de um corpo em trajectória elíptica
Authors: Silva M.F. Ferreira da
Published: November 2011

Em muitos livros de texto, a terceira lei de Kepler é formulada em termos da distância média entre o Sol e cada um dos planetas, não se especificando de que média se trata. Neste trabalho calculam-se três médias diferentes para esta distância, verificando-se que apenas uma é compatível com a referida lei. Adicionalmente, calculam-se e comparam-se as três médias para todas as quantidades físicas relevantes.
Study of acute toxicity and investigation of the presence of β-N-methylamino-L-alanine in the Gunnera manicata L. a species native to Southern Brazil
Authors: Mariotti Kristiane de Cássia , Barreto Fabiano , Schmitt Gabriela Cristina , Zancanaro Ivomar , Dallegrave Eliane , Singer Rodrigo Bustos , Leal Mirna Bainy , Limberger Renata Pereira
Published: October 2011

Gunnera (Gunneraceae) forms a complex association with the cyanobacterium Nostoc puctiforme L. Gunnera-Nostoc symbiosis is the only one reported involving a flowering plant, and results in the formation of the neurotoxic amino acid β-N-methylamino-L-alanine (BMAA). The species Gunnera manicata L., for which phytochemical, pharmacological and toxicological studies are lacking, is found in Southern Brazil. Therefore, acute toxicity and the presence of neurotoxic amino acid were investigated in aqueous extracts of G. manicata. The acute toxicity test was conducted by administering aqueous root extract of G. manicata at a concentration of 2000 mg/kg in a single dose orally to Wistar rats. Lethality was monitored daily for 14 days after treatment. The relative mass of organs was analyzed by one-way ANOVA and macroscopic changes were investigated. The analysis of BMAA, a procedure performed by GC/MS, involved a preliminary derivatization step. The ESI-MS/MS analysis was done by direct infusion. The present study demonstrated absence of neurotoxin in the samples of G. manicata analyzed and absence of acute toxicity in aqueous root extracts. These data confirm that extracts from the roots of G. manicata have a high margin of drug safety.