bluuebunny/crossref_metadata_2025 huggingface dataset:
Extrapolation in the analysis of lung aeration by computed tomography: a validation study
Authors: Reske Andreas W , Rau Anna , Reske Alexander P , Koziol Manja , Gottwald Beate , Alef Michaele , Ionita Jean-Claude , Spieth Peter M , Hepp Pierre , Seiwerts Matthias , Beda Alessandro , Born Silvia , Scheuermann Gerik , Amato Marcelo BP , Wrigge Hermann
Published: November 2011

Introduction

Computed tomography (CT) is considered the gold standard for quantification of global or regional lung aeration and lung mass. Quantitative CT, however, involves the exposure to ionizing radiation and requires manual image processing. We recently evaluated an extrapolation method which calculates quantitative CT parameters characterizing the entire lung from only 10 reference CT-slices thereby reducing radiation exposure and analysis time. We hypothesized that this extrapolation method could be further validated using CT-data from pigs and sheep, which have a different thoracic anatomy.

Methods

We quantified volume and mass of the total lung and differently aerated lung compartments in 168 ovine and 55 porcine whole-lung CTs covering lung conditions from normal to gross deaeration. Extrapolated volume and mass parameters were compared to the respective values obtained by whole-lung analysis. We also tested the accuracy of extrapolation for all possible numbers of CT slices between 15 and 5. Bias and limits of agreement (LOA) were analyzed by the Bland-Altman method.

Results

For extrapolation from 10 reference slices, bias (LOA) for the total lung volume and mass of sheep were 18.4 (-57.2 to 94.0) ml and 4.2 (-21.8 to 30.2) grams, respectively. The corresponding bias (LOA) values for pigs were 5.1 (-55.2 to 65.3) ml and 1.6 (-32.9 to 36.2) grams, respectively. All bias values for differently aerated lung compartments were below 1% of the total lung volume or mass and the LOA never exceeded ± 2.5%. Bias values diverged from zero and the LOA became considerably wider when less than 10 reference slices were used.

Conclusions

The extrapolation method appears robust against variations in thoracic anatomy, which further supports its accuracy and potential usefulness for clinical and experimental application of quantitative CT.
Physiological responses to self-induced burrowing and metabolic rate depression in the ocean quahogArctica islandica
Authors: Strahl Julia , Brey Thomas , Philipp Eva E. R. , Thorarinsdóttir Gudrun , Fischer Natalie , Wessels Wiebke , Abele Doris
Published: November 2011

Arctica islandica is the longest-lived non-colonial animal found so far, and reaches individual ages of 150 years in the German Bight (GB) and more than 350 years around Iceland (IC). Frequent burrowing and physiological adjustments to low tissue oxygenation in the burrowed state are proposed to lower mitochondrial reactive oxygen species (ROS) formation. We investigated burrowing patterns and shell water partial pressure of oxygen (PO2) in experiments with live A. islandica. Furthermore, succinate accumulation and antioxidant defences were recorded in tissues of bivalves in the normoxic or metabolically downregulated state, as well as ROS formation in isolated gills exposed to normoxia, hypoxia and hypoxia/reoxygenation. IC bivalves burrowed more frequently and deeper in winter than in summer under in situ conditions, and both IC and GB bivalves remained burrowed for between 1 and 6 days in laboratory experiments. Shell water PO2 was <5 kPa when bivalves were maintained in fully oxygenated seawater, and ventilation increased before animals entered the state of metabolic depression. Succinate did not accumulate upon spontaneous shell closure, although shell water PO2 was 0 kPa for over 24 h. A ROS burst was absent in isolated gills during hypoxia/reoxygenation, and antioxidant enzyme activities were not enhanced in metabolically depressed clams compared with normally respiring clams. Postponing the onset of anaerobiosis in the burrowed state and under hypoxic exposure presumably limits the need for elevated recovery respiration upon surfacing and oxidative stress during reoxygenation.
Patterns of coral ecological immunology: variation in the responses of Caribbean corals to elevated temperature and a pathogen elicitor
Authors: Palmer Caroline V. , McGinty Elizabeth S. , Cummings David J. , Smith Stephanie M. , Bartels Erich , Mydlarz Laura D.
Published: November 2011

Disease epizootics are increasing with climatic shifts, yet within each system only a subset of species are identified as the most vulnerable. Understanding ecological immunology patterns as well as environmental influences on immune defenses will provide insight into the persistence of a functional system through adverse conditions. Amongst the most threatened ecosystems are coral reefs, with coral disease epizootics and thermal stress jeopardizing their survival. Immune defenses were investigated within three Caribbean corals, Montastraea faveolata, Stephanocoenia intersepta and Porites astreoides, which represent a range of disease and bleaching susceptibilities. Levels of several immune parameters were measured in response to elevated water temperature and the presence of a commercial pathogen-associated molecular pattern (PAMP) – lipopolysaccharide (LPS) – as an elicitor of the innate immune response. Immune parameters included prophenoloxidase (PPO) activity, melanin concentration, bactericidal activity, the antioxidants peroxidase and catalase, and fluorescent protein (FP) concentration. LPS induced an immune response in all three corals, although each species responded differently to the experimental treatments. For example, M. faveolata, a disease-susceptible species, experienced significant decreases in bactericidal activity and melanin concentration after exposure to LPS and elevated temperature alone. Porites astreoides, a disease-resistant species, showed increased levels of enzymatic antioxidants upon exposure to LPS independently and increased PPO activity in response to the combination of LPS and elevated water temperature. This study demonstrates the ability of reef-building corals to induce immune responses in the presence of PAMPs, indicating activation of PAMP receptors and the transduction of appropriate signals leading to immune effector responses. Furthermore, these data address the emerging field of ecological immunology by highlighting interspecific differences in immunity and immunocompetences among Caribbean corals, which are reflected in their life-history characteristics, disease susceptibilities and bleaching-induced mortality.
Apnea stimulates the adaptive response to oxidative stress in elephant seal pups
Authors: Vázquez-Medina José Pablo , Zenteno-Savín Tania , Tift Michael S. , Forman Henry Jay , Crocker Daniel E. , Ortiz Rudy M.
Published: November 2011

Extended breath-hold (apnea) bouts are routine during diving and sleeping in seals. These apneas result in oxygen store depletion and blood flow redistribution towards obligatory oxygen-dependent tissues, exposing seals to critical levels of ischemia and hypoxemia. The subsequent reperfusion/reoxygenation has the potential to increase oxidant production and thus oxidative stress. The contributions of extended apnea to oxidative stress in adapted mammals are not well defined. To address the hypothesis that apnea in seals is not associated with increased oxidative damage, blood samples were collected from northern elephant seal pups (N=6) during eupnea, rest- and voluntary submersion-associated apneas, and post-apnea (recovery). Plasma 4-hydroxynonenal (HNE), 8-isoprostanes (8-isoPGF2α), nitrotyrosine (NT), protein carbonyls, xanthine and hypoxanthine (HX) levels, along with xanthine oxidase (XO) activity, were measured. Protein content of XO, superoxide dismutase 1 (Cu,ZnSOD), catalase and myoglobin (Mb), as well as the nuclear content of hypoxia inducible factor 1α (HIF-1α) and NF-E2-related factor 2 (Nrf2), were measured in muscle biopsies collected before and after the breath-hold trials. HNE, 8-iso PGF2α, NT and protein carbonyl levels did not change among eupnea, apnea or recovery. XO activity and HX and xanthine concentrations were increased at the end of the apneas and during recovery. Muscle protein content of XO, CuZnSOD, catalase, Mb, HIF-1α and Nrf2 increased 25–70% after apnea. Results suggest that rather than inducing the damaging effects of hypoxemia and ischemia/reperfusion that have been reported in non-diving mammals, apnea in seals stimulates the oxidative stress and hypoxic hormetic responses, allowing these mammals to cope with the potentially detrimental effects associated with this condition.
Selective epoxidation of propylene to propylene oxide with H2 and O2 over Au/Ti-MWW catalysts
Authors: Ren Yingjie , Xu Le , Zhang Liyan , Wang Jianggan , Liu Yueming , He Mingyuan , Wu Peng
Published: November 2011

Direct epoxidation of propylene to propylene oxide (PO) with H2 and O2 has been performed on bifunctional catalysts, Au nanoparticles supported on novel Ti-MWW titanosilicate (Au/Ti-MWW). In comparison to conventional Au/TS-1 catalysts, Au/Ti-MWW exhibited a similar phenomenon with respect to PO formation, that is, the PO selectivity increased with increasing Si/Ti ratio of titanosilicate. However, at optimized Ti contents corresponding to Si/Ti ratio >140, the PO selectivity of Au/Ti-MWW catalysts was lower than 60 % in comparison to ca. 90 % achieved on Au/TS-1. A large number of boron species and defect-site-related hydroxyl groups contained in Ti-MWW were assumed to retard the desorption of PO from the channels or crystallite surface of zeolite, which favors side reactions such as over-oxidation and decomposition of PO. Poststructural rearrangement was then carried out on Ti-MWW with piperidine (PI) solution to improve effectively its hydrophobicity, leading to defect-less Re-Ti-MWW. This enhanced significantly the PO selectivity of Au/Re-Ti-MWW thus prepared, which reached as high as 92 % at Si/Ti ratio of 135. Au/Re-Ti-MWW(135) then gave the highest PO formation rate of 22.0 gPO kg–1 h–1.
The Association between Vitamin D Receptor Expression and Prolonged Overall Survival in Breast Cancer
Authors: Ditsch Nina , Toth Bettina , Mayr Doris , Lenhard Miriam , Gallwas Julia , Weissenbacher Tobias , Dannecker Christian , Friese Klaus , Jeschke Udo
Published: November 2011

In this study, we analyzed vitamin D receptor (VDR) expression and survival in a breast cancer patient cohort of 82 breast cancer patients. Immunohistochemical analysis was possible in 91.5% of the patients (75/82). Staining was evaluated using the semi-quantitative assay according to Remmele and Stegner (immunoreactivity score [IRS]). IRS 0–1 was negative/very low, IRS 2–4 was moderate to high, and IRS 6–12 was high. Statistical analysis was performed by Spearman’s correlation test ( p<0.05 significant). Overall survival was analyzed using Kaplan-Meier estimations. Only 6 patients had a negative IRS. Moderate IRS values were present in 20 patients. Most of the patients had a high IRS (49). For survival analysis, data were dichotomized (IRS 0–4: negative to moderate and IRS 6–12: high VDR expression). In univariate analysis, VDR expression showed significant differences in progression-free survival (PFS) and overall survival (OS). Patients with high IRS scores showed significantly better PFS and OS than patients with moderate/negative IRS scores for VDR expression. Tumor size was significantly correlated to PFS. When analyzed separately, the three different IRS groups showed significant differences in VDR expression. The present data suggest that VDR expression in breast cancer tissue may be of clinical significance, and the results provide evidence that VDR may be a factor with prognostic relevance.
Age-related Accumulation of Non-heme Ferric and Ferrous Iron in Mouse Ovarian Stroma Visualized by Sensitive Non-heme Iron Histochemistry
Authors: Asano Yoshiya
Published: November 2011

Sensitive non-heme iron histochemistry—namely, the perfusion-Perls method and perfusion-Turnbull method—was applied to study the distribution and age-related accumulation of non-heme ferric iron and ferrous iron in mouse ovary. Light and electron microscopic studies revealed that non-heme ferric iron is distributed predominantly in stromal tissue, especially in macrophages. By contrast, the distribution of non-heme ferrous iron was restricted to a few ovoid macrophages. Aged ovaries exhibited remarkable non-heme iron accumulation in all stromal cells. In particular, non-heme ferrous iron level was increased in stromal tissue, suggestive of increased levels of redox-active iron, which can promote oxidative stress. Moreover, intense localization of both non-heme ferric and ferrous iron was observed in aggregated large stromal cells that were then characterized as ceroid-laden enlarged macrophages with frothy cytoplasm. Intraperitoneal iron overload in adult mice resulted in non-heme iron deposition in the entire stroma and generation of enlarged macrophages, suggesting that excessive iron accumulation induced macrophage morphological changes. The data indicated that non-heme iron accumulation in ovarian stromal tissue may be related to aging of the ovary due to increasing oxidative stress.
Effects of nimesulide on testicular functions in prepubertal albino rats
Authors: Ugochukwu Agbasi Patrick , Ebere Orisakwe Orish , Okwuoma Abanobi
Published: November 2011

Background: Daily consumption of painkillers has almost become a routine in many parts of Africa and Asia due to manual labor, especially in young adults. In view of the wide-scale use of painkillers in many parts of Africa and Asia, it is feared that the use of nimesulide may constitute an appreciable public health risk. The present work is aimed at assessing the long-term testicular toxicity of nimesulide in growing male albino rats.

Methods: Male albino rats aged 4–5 weeks and weighing between 36 and 42 g were obtained from the Toxicology Unit of the Department of Pharmacology, Faculty of Pharmacy University of Nigeria, Nsukka, Nigeria. The animals were housed singly in a cross-ventilated room at a temperature 22°C±3°C and a 12-h light/12-h dark cycle. They were fed with standard rat pellets (Pfizer Pharmaceuticals, Ikeja, Nigeria) and were given water ad libitum. The rats were divided into three groups of five rats each: the first and second groups orally received 5 and 7.5 mg/kg/day of nimesulide, respectively, whereas the third group did not receive any drug and acted as controls for 56 days. Weekly body weight of each rat was taken. Blood samples were collected on the 56th day by cardiac puncture, and serum samples were frozen until analysis. Rats were sacrificed under ether anesthesia. Epididymal semen number was counted using a Neubauer counting chamber. Sperm motility was assayed microscopically within 5 min at 37°C. Estradiol and testosterone were analyzed with electrochemiluminescence immunoassay using Elecsys autoanalyzer, model 1010 (Roche, Mannheim, Germany). The testes were excised, weighed, and fixed in Bouin fluid and processed for histopathology.

Results: Treatment with nimesulide did not significantly affect body weight, absolute and relative testis weights, or epididymal sperm number, but there were significant differences in testosterone and estradiol levels. At the doses studied, there were no significant changes in testicular architecture except for mild degenerative changes.

Conclusions: In conclusion, nimesulide at normal therapeutic doses may not be spermatoxic, but it is feared that at higher doses, it may have testicular toxicity in albino rats.
Genetic Deletion of Trace Amine 1 Receptors Reveals Their Role in Auto-Inhibiting the Actions of Ecstasy (MDMA)
Authors: Di Cara Benjamin , Maggio Roberto , Aloisi Gabriella , Rivet Jean-Michel , Lundius Ebba Gregorsson , Yoshitake Takashi , Svenningsson Per , Brocco Mauricette , Gobert Alain , De Groote Lotte , Cistarelli Laetitia , Veiga Sylvie , De Montrion Catherine , Rodriguez Marianne , Galizzi Jean-Pierre , Lockhart Brian P. , Cogé Francis , Boutin Jean A. , Vayer Philippe , Verdouw P. Monika , Groenink Lucianne , Millan Mark J.
Published: November 2011

“Ecstasy” [3,4-methylenedioxymetamphetamine (MDMA)] is of considerable interest in light of its prosocial properties and risks associated with widespread recreational use. Recently, it was found to bind trace amine-1 receptors (TA1Rs), which modulate dopaminergic transmission. Accordingly, using mice genetically deprived of TA1R (TA1-KO), we explored their significance to the actions of MDMA, which robustly activated human adenylyl cyclase-coupled TA1R transfected into HeLa cells. In wild-type (WT) mice, MDMA elicited a time-, dose-, and ambient temperature-dependent hypothermia and hyperthermia, whereasTA1-KOmice displayed hyperthermia only. MDMA-induced increases in dialysate levels of dopamine (DA) in dorsal striatum were amplified inTA1-KOmice, despite identical levels of MDMA itself. A similar facilitation of the influence of MDMA upon dopaminergic transmission was acquired in frontal cortex and nucleus accumbens, and induction of locomotion by MDMA was haloperidol-reversibly potentiated inTA1-KOversus WT mice. Conversely, genetic deletion of TA1R did not affect increases in DA levels evoked by para-chloroamphetamine (PCA), which was inactive at hTA1sites. The TA1R agonisto-phenyl-3-iodotyramine (o-PIT) blunted the DA-releasing actions of PCA bothin vivo(dialysis) andin vitro(synaptosomes) in WT but notTA1-KOanimals. MDMA-elicited increases in dialysis levels of serotonin (5-HT) were likewise greater inTA1-KOversus WT mice, and 5-HT-releasing actions of PCA were bluntedin vivoandin vitrobyo-PIT in WT mice only. In conclusion, TA1Rs exert an inhibitory influence on both dopaminergic and serotonergic transmission, and MDMA auto-inhibits its neurochemical and functional actions by recruitment of TA1R. These observations have important implications for the effects of MDMA in humans.
CBP in the Nucleus Accumbens Regulates Cocaine-Induced Histone Acetylation and Is Critical for Cocaine-Associated Behaviors
Authors: Malvaez Melissa , Mhillaj Emanuela , Matheos Dina P. , Palmery Maura , Wood Marcelo A.
Published: November 2011

Cocaine exposure triggers molecular events that lead to long-lasting changes in brain structure and function. These changes can lead to the development of persistent and robust behavioral adaptations that characterize addiction. Recent evidence suggests the regulation of transcription via chromatin modification, such as histone acetylation, has an important role in the development of addictive behavior. Histone acetylation is regulated by histone acetyltransferases (HATs), which acetylate histones and promote transcription, and histone deacetylases (HDACs), which remove acetyl groups and silence transcription. Studies have demonstrated that HDACs may negatively regulate cocaine-induced behaviors, but very little is known about the role of specific HATs in long-lasting drug-induced plasticity. The histone acetyltransferase CREB-binding protein (CBP) mediates transcriptional activation by recruiting basal transcription machinery and acetylating histones. CBP is a critically important chromatin-modifying enzyme involved in regulating gene expression required for long-term plasticity and memory. However, the role of CBP in cocaine-induced behaviors remains largely unknown. We examined the role of CBP in drug-induced plasticity using CBP-FLOX genetically modified mice in combination with adeno-associated virus expressing Cre-recombinase to generate focal homozygous deletions ofCbpin the nucleus accumbens (NAc). A complete loss of CBP in NAc neurons results in decreased histone acetylation and significantly altered c-fosexpression in response to cocaine. Furthermore, the deletion of CBP in the NAc correlates with significant impairments in cocaine sensitivity and context–cocaine associated memory. This is the first study to demonstrate a definitive role for CBP in modulating gene expression that may subserve drug-seeking behaviors.
Sodium-Dependent Vitamin C Transporter 2 Deficiency Causes Hypomyelination and Extracellular Matrix Defects in the Peripheral Nervous System
Authors: Gess Burkhard , Röhr Dominik , Fledrich Robert , Sereda Michael W. , Kleffner Ilka , Humberg Anne , Nowitzki Johanna , Strecker Jan-Kolja , Halfter Hartmut , Young Peter
Published: November 2011

Ascorbic acid (vitamin C) is necessary for myelination of Schwann cell/neuron cocultures and has shown beneficial effects in the treatment of a Charcot-Marie-Tooth neuropathy 1A (CMT1A) mouse model. Although clinical studies revealed that ascorbic acid treatment had no impact on CMT1A, it is assumed to have an important function in peripheral nerve myelination and possibly in remyelination. However, the transport pathway of ascorbic acid into peripheral nerves and the mechanism of ascorbic acid function in peripheral nervesin vivoremained unclear.

In this study, we used sodium-dependent vitamin C transporter 2-heterozygous (SVCT2+/−) mice to elucidate the functions of SVCT2 and ascorbic acid in the murine peripheral nervous system. SVCT2 and ascorbic acid levels were reduced in SVCT2+/−peripheral nerves. Morphometry of sciatic nerve fibers revealed a decrease in myelin thickness and an increase in G-ratios in SVCT2+/−mice. Nerve conduction velocities and sensorimotor performance in functional tests were reduced in SVCT2+/−mice. To investigate the mechanism of ascorbic acid function, we studied the expression of collagens in the extracellular matrix of peripheral nerves. Here, we show that expression of various collagen types was reduced in sciatic nerves of SVCT2+/−mice. We found that collagen gene transcription was reduced in SVCT2+/−mice but hydroxyproline levels were not, indicating that collagen formation was regulated on the transcriptional and not the posttranslational level. These results help to clarify the transport pathway and mechanism of action of ascorbic acid in the peripheral nervous system and may lead to novel therapeutic approaches to peripheral neuropathies by manipulation of SVCT2 function.
Hydrodynamic Cellular Volume Changes Enable Glioma Cell Invasion
Authors: Watkins Stacey , Sontheimer Harald
Published: November 2011

Malignant gliomas are highly invasive brain tumors that currently lack effective treatment. Unlike other cancers, gliomas do not metastasize via the vasculature but invade surrounding brain solely along extracellular routes, primarily moving along the vasculature and nerve tracts. This study uses several model systems to visualize and quantitatively assess cell volume changes of human glioma cells invading within the brain's extracellular space of C.B.17 severe combined immunodeficient (scid) mice and tumor cells invading in a modified Boyden chamber using three-dimensional multiphoton and confocal time-lapse microscopy. Regardless of model system used to quantitatively assess volume changes, invading glioma cells maximally decreased their volume by 30–35%, a value that was independent of barrier and cell size. Through osmotic challenges, we demonstrate that the observed cellular volume changes during invasion represent the smallest achievable cell volume and require glioma cells to release all free unbound cytoplasmic water. Water osmotically follows the release of Cl−through ion channels and cotransporters and blockade of Cl−flux inhibits both volume changes and cell invasion. Hence, invading glioma cells use hydrodynamic volume changes to meet the spatial constraints imposed within the brain, using essentially all free, unbound cytoplasmic water to maximally alter their volume as they invade.
Calcium/Calmodulin Kinase II in the Pedunculopontine Tegmental Nucleus Modulates the Initiation and Maintenance of Wakefulness
Authors: Datta Subimal , O'Malley Matthew W. , Patterson Elissa H.
Published: November 2011

The pedunculopontine tegmentum nucleus (PPT) is critically involved in the regulation of wakefulness (W) and rapid eye movement (REM) sleep, but our understanding of the mechanisms of this regulation remains incomplete. The present study was designed to determine the role of PPT intracellular calcium/calmodulin kinase (CaMKII) signaling in the regulation of W and sleep. To achieve this aim, three different concentrations (0.5, 1.0, and 2.0 nmol) of the CaMKII activation inhibitor, KN-93, were microinjected bilaterally (100 nl/site) into the PPT of freely moving rats, and the effects on W, slow-wave sleep (SWS), REM sleep, and levels of phosphorylated CaMKII (pCaMKII) expression in the PPT were quantified. These effects, which were concentration-dependent and affected wake–sleep variables for 3 h, resulted in decreased W, due to reductions in the number and duration of W episodes; increased SWS and REM sleep, due to increases in episode duration; and decreased levels of pCaMKII expression in the PPT. Regression analyses revealed that PPT levels of pCaMKII were positively related with the total percentage of time spent in W (R2= 0.864;n= 28 rats;p< 0.001) and negatively related with the total percentage of time spent in sleep (R2= 0.863;p< 0.001). These data provide the first direct evidence that activation of intracellular CaMKII signaling in the PPT promotes W and suppresses sleep. These findings are relevant for designing a drug that could treat excessive sleepiness by promoting alertness.
PALS1 Is Essential for Retinal Pigment Epithelium Structure and Neural Retina Stratification
Authors: Park Bokyung , Alves Celso Henrique , Lundvig Ditte M. , Tanimoto Naoyuki , Beck Susanne C. , Huber Gesine , Richard Fabrice , Klooster Jan , Andlauer Till F. M. , Swindell Eric C. , Jamrich Milan , Le Bivic André , Seeliger Mathias W. , Wijnholds Jan
Published: November 2011

The membrane-associated palmitoylated protein 5 (MPP5 or PALS1) is thought to organize intracellular PALS1-CRB-MUPP1 protein scaffolds in the retina that are involved in maintenance of photoreceptor–Müller glia cell adhesion. In humans, the Crumbs homolog 1 (CRB1) gene is mutated in progressive types of autosomal recessive retinitis pigmentosa and Leber congenital amaurosis. However, there is no clear genotype–phenotype correlation forCRB1mutations, which suggests that other components of the CRB complex may influence the severity of retinal disease. Therefore, to understand the physiological role of the Crumbs complex proteins, especially PALS1, we generated and analyzed conditional knockdown mice forPals1. Small irregularly shaped spots were detected throughout the PALS1 deficient retina by confocal scanning laser ophthalmoscopy and spectral domain optical coherence tomography. The electroretinography a- and b-wave was severely attenuated in the aged mutant retinas, suggesting progressive degeneration of photoreceptors. The histological analysis showed abnormal retinal pigment epithelium structure, ectopic photoreceptor nuclei in the subretinal space, an irregular outer limiting membrane, half rosettes of photoreceptors in the outer plexiform layer, and a thinner photoreceptor synaptic layer suggesting improper photoreceptor cell layering during retinal development. The PALS1 deficient retinas showed reduced levels of Crumbs complex proteins adjacent to adherens junctions, upregulation of glial fibrillary acidic protein indicative of gliosis, and persisting programmed cell death after retinal maturation. The phenotype suggests important functions of PALS1 in the retinal pigment epithelium in addition to the neural retina.
Impact of ethnicity on gestational diabetes identified with the WHO and the modified International Association of Diabetes and Pregnancy Study Groups criteria: a population-based cohort study
Authors: Jenum Anne K , Mørkrid Kjersti , Sletner Line , Vange Siri , Torper Johan L , Nakstad Britt , Voldner Nanna , Rognerud-Jensen Odd H , Berntsen Sveinung , Mosdøl Annhild , Skrivarhaug Torild , Vårdal Mari H , Holme Ingar , Yajnik Chittaranjan S , Birkeland Kåre I
Published: November 2011

Objective

The International Association of Diabetes and Pregnancy Study Groups (IADPSG) recently proposed new criteria for diagnosing gestational diabetes mellitus (GDM). We compared prevalence rates, risk factors, and the effect of ethnicity using the World Health Organization (WHO) and modified IADPSG criteria.

Methods

This was a population-based cohort study of 823 (74% of eligible) healthy pregnant women, of whom 59% were from ethnic minorities. Universal screening was performed at 28±2 weeks of gestation with the 75 g oral glucose tolerance test (OGTT). Venous plasma glucose (PG) was measured on site. GDM was diagnosed as per the definition of WHO criteria as fasting PG (FPG) ≥7.0 or 2-h PG ≥7.8 mmol/l; and as per the modified IADPSG criteria as FPG ≥5.1 or 2-h PG ≥8.5 mmol/l.

Results

OGTT was performed in 759 women. Crude GDM prevalence was 13.0% with WHO (Western Europeans 11%, ethnic minorities 15%,P=0.14) and 31.5% with modified IADPSG criteria (Western Europeans 24%, ethnic minorities 37%,P< 0.001). Using the WHO criteria, ethnic minority origin was an independent predictor (South Asians, odds ratio (OR) 2.24 (95% confidence interval (CI) 1.26–3.97); Middle Easterners, OR 2.13 (1.12–4.08)) after adjustments for age, parity, and prepregnant body mass index (BMI). This increased OR was unapparent after further adjustments for body height (proxy for early life socioeconomic status), education and family history of diabetes. Using the modified IADPSG criteria, prepregnant BMI (1.09 (1.05–1.13)) and ethnic minority origin (South Asians, 2.54 (1.56–4.13)) were independent predictors, while education, body height and family history had little impact.

Conclusion

GDM prevalence was overall 2.4-times higher with the modified IADPSG criteria compared with the WHO criteria. The new criteria identified many subjects with a relatively mild increase in FPG, strongly associated with South Asian origin and prepregnant overweight.
A novel human Smad4 mutation is involved in papillary thyroid carcinoma progression
Authors: D'Inzeo Sonia , Nicolussi Arianna , Donini Caterina Francesca , Zani Massimo , Mancini Patrizia , Nardi Francesco , Coppa Anna
Published: November 2011

Smad proteins are the key effectors of the transforming growth factor β (TGFβ) signaling pathway in mammalian cells. Smad4 plays an important role in human physiology, and its mutations were found with high frequency in wide range of human cancer. In this study, we have functionally characterized Smad4 C324Y mutation, isolated from a nodal metastasis of papillary thyroid carcinoma. We demonstrated that the stable expression of Smad4 C324Y in FRTL-5 cells caused a significant activation of TGFβ signaling, responsible for the acquisition of transformed phenotype and invasive behavior. The coexpression of Smad4 C324Y with Smad4 wild-type determined an increase of homo-oligomerization of Smad4 with receptor-regulated Smads and a lengthening of nuclear localization. FRTL-5 clones overexpressing Smad4 C324Y showed a strong reduction of response to antiproliferative action of TGFβ1, acquired the ability to grow in anchorage-independent conditions, showed a fibroblast-like appearance and a strong reduction of the level of E-cadherin, one crucial event of the epithelial–mesenchymal transition process. The acquisition of a mesenchymal phenotype gave the characteristics of increased cellular motility and a significant reduction in adhesion to substrates such as fibronectin and laminin. Overall, our results demonstrate that the Smad4 C324Y mutation plays an important role in thyroid carcinogenesis and can be considered as a new prognostic and therapeutic target for thyroid cancer.
Clinical picture and treatment of jet lag
Authors: Igaz Péter , Tulassay Zsolt
Published: November 2011

Symptoms associated with rapid time zone crosses represent one of the major health problems associated with commercial flights. This condition is termed jet lag that is characterized by sleep disturbances (insomnia, sleepiness), somatic symptoms, and decrease in mental and physical outputs. Difference between the light-darkness cycles of the destination and internal homeostatic rhythm is responsible for the syndrome. Restitution of the internal rhythm by appropriate light exposure or melatonin, optimal sleep time and duration, and drugs can be used in its treatment. Orv. Hetil., 2011, 152, 2021–2024.
Broccoli yield in response to top-dressing fertilization with green manure and biofertilizer
Authors: Freitas Gilberto Bernardo de , Rocha Márcio Sousa , Santos Ricardo Henrique Silva , Freitas Letícia Monteiro da Silva , Resende Leandro de Almeida
Published: November 2011

The objective of this work was to evaluate the productive performance of broccoli under different top-dressing organic fertilizations. The experiment was conducted under protected cultivation, in a completely randomized design with four replications, with two plants per experimental unit. Broccoli seedlings were produced in a commercial substrate in styrofoam trays. The seedlings were transplanted to plastic pots containing 10.0 L of substrate made up of subsoil and organic compost at the ratio of 3:1 (v/v), respectively, which is equivalent to about 20.0 t ha-1 of organic compost at planting. After seedling establishment, the top-dressing fertilization treatments were applied: gliricidia biomass associated or not with liquid biofertilizer of cattle manure to the soil and bokashi. Two control treatments were established: one with mineral fertilization recommended for the crop and the other without top-dressing fertilization. The broccoli production was evaluated (commercial standard). Plants that received mineral fertilizer were more productive, however, they were not significantly different (p>0.05), by Dunnet test, from the plants fertilized with 2.5 t ha-1 gliricidiabiomass (dry mass) associated with liquid biofertilizer (2.0 L m-2) applied to soil. Top-dressing fertilizations with only gliricidia, at 2.5 and 5.0 t ha-1 of biomass (dry mass), resulted in no significant increase in production of broccoli inflorescence. The use of bokashi in addition to gliricidia biomass and liquid biofertilizer reduced the efficiency of the fertilization compared with plants that received only gliricidia and liquid biofertilizer.
Determinantes do déficit estatural em menores de cinco anos no Estado de Pernambuco
Authors: Menezes Risia Cristina Egito de , Lira Pedro Israel Cabral de , Leal Vanessa Sá , Oliveira Juliana Souza , Santana Sandra Cristina da Silva , Sequeira Leopoldina Augusta de Souza , Rissin Anete , Batista Filho Malaquias
Published: November 2011

OBJETIVO: Descrever o déficit estatural de menores de cinco anos e identificar fatores associados. MÉTODOS: Estudo transversal de base populacional realizado em 1991, 1997 e 2006 no Estado de Pernambuco. A análise da prevalência e fatores associados ao déficit estatural (altura para idade < -2 escore Z) incluiu: condições socioeconômicas, características maternas e da criança e de assistência à saúde. A regressão logística múltipla utilizou o modelo hierarquizado, para avaliar o impacto das variáveis explanatórias sobre o déficit de estatura das crianças. RESULTADOS: A prevalência da desnutrição em crianças pelo índice altura para idade diminuiu 65% entre 1991 e 2006. As variáveis socioeconômicas (renda familiar per capita, escolaridade materna, número de pessoas na residência e acesso a bens de consumo), a altura materna e o peso ao nascer permaneceram entre os fatores associados ao déficit estatural das crianças. CONCLUSÕES: Todos os determinantes analisados melhoraram no período analisado, nem sempre de forma igualitária. Apesar da redução expressiva da desnutrição nas crianças pernambucanas, ainda existem diferenciais em relação ao déficit de estatura, sendo mais favoráveis para as crianças em melhores condições socioeconômicas.
Fatores associados com a qualidade de vida relacionada à saúde de idosos em hemodiálise
Authors: Braga Sonia Faria Mendes , Peixoto Sérgio Viana , Gomes Isabel Cristina , Acúrcio Francisco de Assis , Andrade Eli Iola Gurgel , Cherchiglia Mariângela Leal
Published: November 2011

OBJETIVO: Identificar fatores associados à qualidade de vida relacionada à saúde de pacientes idosos em hemodiálise. MÉTODOS: Estudo transversal com 223 pacientes com idade > 60 anos em hemodiálise nas unidades de diálise do município de Belo Horizonte, MG, em 2008. A qualidade de vida foi avaliada utilizando o Kidney Disease and Quality of Life - Short Form (KDQOL-SF) e o Medical Outcome Survey - Short Form 36 (SF-36). Os três escores do KDQOL-SF medidos foram: componente da doença renal sumarizado (11 subescalas), componente físico sumarizado (quatro subescalas) e componente mental sumarizado (quatro subescalas). RESULTADOS: Foram observadas associações negativas significativas e independentes do componente da doença renal e mental com número de doenças crônicas e tempo de tratamento (ambas). O componente físico foi menor entre os mais velhos, as mulheres, aqueles com maior número de internações e com três ou mais doenças crônicas. CONCLUSÕES: A associação consistente com presença de doenças crônicas mostra a importância do perfil de morbidade para a qualidade de vida dessa população. A identificação dos fatores associados, como aumento da idade, sexo feminino, número de internações e tempo de tratamento, pode favorecer o planejamento adequado das ações de saúde para melhor atender a esse grupo.
Freqüência e padrão da violência por parceiro íntimo antes, durante e depois da gravidez
Authors: Silva Elisabete Pereira , Ludermir Ana Bernarda , Araújo Thália Velho Barreto de , Valongueiro Sandra Alves
Published: November 2011

OBJETIVO: Estimar a prevalência e analisar o padrão da violência por parceiro íntimo antes e durante a gestação e no pós-parto. MÉTODOS: Estudo de coorte realizado com 960 mulheres de 18 a 49 anos, cadastradas no Programa Saúde da Família da cidade do Recife, PE, entre 2005 e 2006. As mulheres foram entrevistadas durante a gestação e no puerpério, utilizando-se um questionário adaptado do Estudo Multipaíses sobre a Saúde da Mulher e Violência Doméstica da Organização Mundial da Saúde. Para avaliar o padrão de ocorrência da violência por parceiro íntimo, entre um determinado período e o subseqüente, o odds ratio foi calculado com intervalos de 95% de confiança (IC95%). RESULTADOS: A prevalência de violência por parceiro íntimo antes, durante e/ou depois da gestação foi estimada em 47,4% e, para cada período isolado, em 32,4%, 31,0% e 22,6%, respectivamente. As mulheres que relataram violência antes da gravidez tiveram chance 11,6 vezes maior (IC95%: 8,3;16,2) de relatar violência durante a gravidez. Quando as mulheres relataram violência durante a gravidez, a chance de relatos no pós-parto foi 8,2 vezes maior (IC95%: 5,1;11,7). A violência psicológica foi a de maior prevalência, principalmente durante a gestação (28,8%; IC95%: 26,0%;31,7%); a sexual, a menos prevalente, especialmente no pós-parto (3,7%; IC95%: 2,6%;5,0%); e a física diminuiu quase 50% durante a gestação em comparação com o período anterior. CONCLUSÕES: Parcela significativa das mulheres em idade reprodutiva vivencia situações de violência por parceiro íntimo. Os períodos de consultas de pré-natal e de puericultura são oportunidades para que o profissional de saúde possa identificar situações de violência.
Tendência da mortalidade por câncer nas capitais e interior do Brasil entre 1980 e 2006
Authors: Silva Gulnar Azevedo e , Gamarra Carmen Justina , Girianelli Vania Reis , Valente Joaquim Gonçalves
Published: November 2011

OBJETIVO: Analisar a tendência corrigida da mortalidade geral por câncer e principais tipos nas capitais e demais municípios do Brasil entre 1980 e 2006. MÉTODOS: Os dados sobre óbitos (n = 2.585.012) decorrentes de câncer entre 1980 e 2006 foram obtidos no Sistema de Informações sobre Mortalidade, e os demográficos, no Instituto Brasileiro de Geografia e Estatística. As taxas de mortalidade geral por câncer e principais tipos foram corrigidas redistribuindo proporcionalmente 50% das mortes mal definidas e padronizando-as por idade segundo população padrão mundial. As curvas de tendência para o Brasil e grandes regiões foram calculadas para capitais e demais municípios segundo sexo e avaliadas por meio de regressão linear simples. RESULTADOS: Entre os homens, as taxas de mortalidade para os cânceres de pulmão, próstata e colo-retal foram ascendentes; declinantes para o de estômago e estáveis para o de esôfago. Entre as mulheres, houve aumento da mortalidade por câncer de mama, pulmão e colo-retal; e diminuição das taxas para os cânceres de colo do útero e de estômago. A evolução da mortalidade variou entre as regiões do País, com padrões distintos entre as capitais e demais municípios. CONCLUSÕES: A correção das taxas de mortalidade com redistribuição dos óbitos mal definidos aumentou a magnitude da mortalidade geral por câncer no Brasil em cerca de 10% em 1980 e 5% em 2006. Nos municípios do interior não se observou tendência à queda ou estabilidade como nas capitais. Menor alcance das ações de prevenção e a dificuldade de acesso a serviços de diagnóstico e tratamento para câncer para a população residente fora dos grandes centros urbanos podem explicar, em parte, essas diferenças.
Fungemia in a university hospital: an epidemiological approach
Authors: Couto Fabíola Maria Marques do , Macedo Daniele Patrícia Cerqueira , Neves Rejane Pereira
Published: November 2011

INTRODUCTION: Fungemia corresponds to the isolation of fungi in the bloodstream and occurs mostly in immunosuppressed patients. The early diagnosis and treatment of these infections are relevant given the serious threat to the affected patients and possible spread to other organs, often becoming fatal. The growing number of fungemia associated with poor prognosis resulted in this research aiming to diagnose and assess the epidemiological aspects of hematogenous infections by fungi. METHODS: The study included 58 blood samples collected within a 1-year period, from patients at the Hospital das Clinicas, Federal University of Pernambuco, by venipuncture in vacuum tubes. Blood samples were processed for direct examination and culture and identification, conducted by observing the macroscopic and microscopic characteristics, as well as physiological characteristics when necessary. RESULTS: Eight (13.8%) episodes of fungemia were identified, accounting for the total sample, and these pathogens were Candida, Histoplasma, Trichosporon, Cryptococcus, and a dematiaceous fungus. C. albicans was the prevalent species, accounting for 37.5% of the cases. Most affected patients were adult males. There was no predominance for any activity, and the risk of acquired immunodeficiency syndrome was the underlying pathology most often cited. CONCLUSIONS: The isolation of fungi considered as emergent species, such as C. membranifaciens and dematiaceous species, highlights the importance of epidemiological monitoring of cases of fungemia in immunocompromised patients, as the therapy of choice depends on the knowledge of the aethiological agent.
Dinâmica celular e microbiológica do leite de ovelhas Santa Inês acompanhadas durante a lactação
Authors: Guaraná Eduardo Levi de Sousa , Santos Rogério Adriano dos , Campos Anne Grace S. Siqueira , Silva Natália da Silva e , Afonso José Augusto Bastos , Mendonça Carla Lopes de
Published: November 2011

Objetivou-se neste estudo, avaliar a dinâmica da infecção intramamária de ovelhas por meio da avaliação clínica, da contagem de células somáticas e do isolamento de bactérias envolvidas na infecção mamária ao longo de toda a lactação, bem como o perfil de sensibilidade destes isolados frente a antimicrobianos. Foram avaliadas 34 ovelhas da raça Santa Inês criadas em sistema semi-intensivo e submetidas ao mesmo manejo higiênico-sanitário e nutricional acompanhadas antes e durante o período de lactação: aproximadamente 10 dias que precedeu ao parto, 15 dias pós-parto (dpp), 30 dpp, 60 dpp e 90 dpp (secagem). Nestes momentos foi realizado o exame clínico da glândula. A contagem de células somáticas (CCS) e o CMT foram realizados nos momentos seguintes ao parto (15dpp, 30dpp, 60dpp e 90dpp), assim como a análise bacteriológica, realizada além dos momentos citados anteriormente, também no momento que precedeu ao parto. A colheita do leite foi realizada por ordenha manual. Todas as ovelhas foram submetidas à sorologia para lentivírus. Os dados da variável CCS foram submetidos ao teste de normalidade segundo Kolmogorov-Smirnov e por não atender a premissa de normalidade, foram transformados em log de base 10 (Log10). Por conseguinte efetuou-se a análise de variância e contraste de médias pelo teste de Tukey com nível de significância de P<0,05. Foi realizado o estudo descritivo das variáveis empregando-se a distribuição de frequências (%). O valor médio da CCS das glândulas não reagentes ao CMT, ao longo do período de lactação, variou de 387.896,08 células/mL a 620.611,11 células/mL e nas glândulas reagentes, dependendo do escore do CMT, apresentou valores médios que variaram de 2.133.914,19 células/mL a 6.730.514,50 células/mL, sem contudo sofrer influência das diferentes fases da lactação. Os resultados obtidos permitiram concluir que a mastite subclínica representa uma preocupação sanitária na criação de ovelhas Santa Inês, chamando-se atenção para o período que precede o parto devido o alto percentual de isolamento bacteriano em glândulas aparentemente sadias, bem como a elevada frequência de isolamento, particularmente de Staphylococcus coagulase-negativo no primeiro mês de lactação
Serogroups and virulence genes of Escherichia coli isolated from psittacine birds
Authors: Knöbl Terezinha , Saidenberg André B.S , Moreno Andrea M , Gomes Tânia A.T , Vieira Mônica A.M , Leite Domingos S , Blanco Jesus E , Ferreira Antônio J.P
Published: November 2011

Escherichia coli isolates from 24 sick psittacine birds were serogrouped and investigated for the presence of genes encoding the following virulence factors: attaching and effacing (eae), enteropathogenic E. coli EAF plasmid (EAF), pili associated with pyelonephritis (pap), S fimbriae (sfa), afimbrial adhesin (afa), capsule K1 (neu), curli (crl, csgA), temperature-sensitive hemagglutinin (tsh), enteroaggregative heat-stable enterotoxin-1 (astA), heat-stable enterotoxin -1 heat labile (LT) and heat stable (STa and STb) enterotoxins, Shiga-like toxins (stx1 and stx2), cytotoxic necrotizing factor 1 (cnf1), haemolysin (hly), aerobactin production (iuc) and serum resistance (iss). The results showed that the isolates belonged to 12 serogroups: O7; O15; O21; O23; O54; O64; O76; O84; O88; O128; O152 and O166. The virulence genes found were: crl in all isolates, pap in 10 isolates, iss in seven isolates, csgA in five isolates, iuc and tsh in three isolates and eae in two isolates. The combination of virulence genes revealed 11 different genotypic patterns. All strains were negative for genes encoding for EAF, EAEC, K1, sfa, afa, hly, cnf, LT, STa, STb, stx1 and stx2. Our findings showed that some E. coli isolated from psittacine birds present the same virulence factors as avian pathogenic E. coli (APEC), uropathogenic E. coli (UPEC) and Enteropathogenic E. coli (EPEC) pathotypes.
Detection of rabies virus nucleoprotein-RNA in several organs outside the Central Nervous System in naturally-infected vampire bats
Authors: Vieira Luiz F. P , Pereira Sílvia R.F.G , Galante Aline C , Castilho Juliana G , Oliveira Rafael N , Brandão Paulo E , Kotait Ivanete
Published: November 2011

Rabies is a neurological disease, but the rabies virus spread to several organs outside the central nervous system (CNS). The rabies virus antigen or RNA has been identified from the salivary glands, the lungs, the kidneys, the heart and the liver. This work aimed to identify the presence of the rabies virus in non-neuronal organs from naturally-infected vampire bats and to study the rabies virus in the salivary glands of healthy vampire bats. Out of the five bats that were positive for rabies in the CNS, by fluorescent antibody test (FAT), viral isolation in N2A cells and reverse transcription - polymerase chain reaction (RT-PCR), 100% (5/5) were positive for rabies in samples of the tongue and the heart, 80% (4/5) in the kidneys, 40% (2/5) in samples of the salivary glands and the lungs, and 20% (1/5) in the liver by RT-PCR test. All the nine bats that were negative for rabies in the CNS, by FAT, viral isolation and RT-PCR were negative for rabies in the salivary glands by RT-PCR test. Possible consequences for rabies epidemiology and pathogenesis are discussed in this work.