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Terms modified by Unclear Selected AbstractsMeconium aspiration syndrome: a role for phospholipase A2 in the pathogenesis?ACTA PAEDIATRICA, Issue 4 2001P KääpäArticle first published online: 2 JAN 200 The pathophysiology of neonatal meconium aspiration syndrome (MAS), often resulting in severe respiratory failure, is complex and still largely unclear. Factors involved in the propagation of acute lung injury after perinatal aspiration of meconium include obstruction of the airways, ventilation/perfusion mismatch, increase of the pulmonary vascular resistance and a rapidly developing parenchymal and alveolar inflammatory reaction with associated surfactant dysfunction. Conclusion: Although the early pulmonary inflammatory response is believed to play a central pathogenetic role in the meconium-induced acute lung damage, its initiating mechanisms are still poorly defined. However, increasing evidence indicates a direct toxic effect of meconium. [source] Development of olfactory epithelium in the human fetus: Scanning electron microscopic observationsCONGENITAL ANOMALIES, Issue 3 2009Mitsuhiro Kimura ABSTRACT Aims:, Human olfactory epithelium becomes functional at birth, but prenatal development remains unclear. In the present study, we aimed to clarify the development of human olfactory epithelium using scanning electron microscopy (SEM). Methods:, The development of human olfactory epithelium was observed in 24 externally normal fetuses, which were formalin-fixed and long-preserved, with a crown-rump length (CRL) of 102,336 mm (gestational week 14,38). The olfactory mucosa in the superior wall of the nasal septum near the choana were dissected and observed under SEM. We examined the number of olfactory vesicles per unit area, diameter of olfactory vesicles, and number and length of cilia on olfactory vesicles. Results:, At circa (ca) CRL 100 mm (ca 14 weeks), olfactory epithelium displayed several olfactory vesicles with 1,2 short cilia per unit area. At ca CRL 150 mm (ca 18 weeks), olfactory vesicles were present in small clusters, and cilia were longer. At CRL lager than 225 mm (ca 26 weeks), olfactory vesicles became located separately from each other, while length and number of cilia per olfactory vesicle were further increased. Conclusion:, The present findings suggest that fetal olfactory epithelium becomes morphologically almost the same as that in adults in late gestation, much later than previously thought. [source] Heart changes in 17-day-old fetuses of diabetic ICR (Institute of Cancer Research) mothers: Improvement with maternal immune stimulationCONGENITAL ANOMALIES, Issue 1 2009Juan Claudio Gutierrez ABSTRACT Maternal diabetes mellitus is associated with increased fetal teratogenesis, including cardiovascular defects. Non-specific maternal immune stimulation with Freund's complete adjuvant (FCA) or interferon gamma (IFN,) has been associated with protection against birth malformations. Using a diabetic mouse model, late-gestation fetal heart and great vessel morphology were analyzed. Four groups of mice were used: non-diabetic females as a control group, hyperglycemic females induced by streptozotocin as a diabetic group, and diabetic females injected either with FCA or IFN,. At day 17 of gestation, females were euthanized and one fetus was arbitrarily selected per litter for fixation and sectioning. Treatment-induced changes in cardiac development were assessed from digital images of serial sections taken at standardized levels in the thorax. One-way parametric and non-parametric ANOVA and ordinal logistic regression were performed to compare the difference among groups (P < 0.05). Maternal hyperglycemia altered morphology of the late-gestation fetal mouse heart by causing ventricular chamber dilation, sectional myocardial reduction, and an increase in transversal aortic area. FCA protected the fetal heart from cavitary dilation in diabetic mothers. FCA and IFN, protected the fetal heart against reduction of myocardial area, and ascending thoracic aorta dilation. Consequences of late gestation heart chamber dilation and myocardial reduction are not yet known. Maternal immune stimulation partially protected against these developmental defects by mechanisms that remain unclear. [source] Gene expression analyses on embryonic external genitalia: identification of regulatory genes possibly involved in masculinization processesCONGENITAL ANOMALIES, Issue 2 2008Hisayo Nishida ABSTRACT Androgen plays a crucial role in initiating and maintaining the expression of male sexual characteristics in mammals. In humans and mice, any defects along the pathway of androgen functions result in congenital urogenital abnormalities. The genital tubercle (GT), an anlage of the external genitalia, differentiates into a penis in males and a clitoris in females. Although masculinization of the external genitalia is androgen-dependent, the molecular pathway of its potential downstream genes is largely unclear. To identify the genes involved in mouse GT masculinization, we performed gene expression analyses, such as real-time quantitative polymerase chain reaction and section in situ hybridization analysis. From our studies we have identified candidate genes, Cyp1b1, Fkbp51 and MafB as potential androgen targets during mouse GT masculinization. [source] Cell death in normal and abnormal developmentCONGENITAL ANOMALIES, Issue 1 2008Philip E. Mirkes ABSTRACT Research over the past 50 years has consistently documented that cell death is an integral part of both normal development and the etiology of birth defects; however, the significance of this cell death has been, until recently, unclear. Research published during the past 15 years has now shown that programmed cell death (PCD) and teratogen-induced cell death are genetically controlled processes (apoptosis) that play important roles in both normal and abnormal development. Therefore, the purpose of this review is to highlight what is known about PCD and teratogen-induced cell death and their relationships to the mechanisms of apoptosis and abnormal development. [source] Maternal environment affects endogenous virus induction in the offspring of type 1 diabetes model non-obese diabetic miceCONGENITAL ANOMALIES, Issue 3 2005Yukiko Kagohashi ABSTRACT Type 1 diabetes results from the destruction of pancreatic b-cells (insulitis). It is a multifactorial disease involving genetic and environmental factors, including the maternal environment. Viruses have also been implicated in the pathogenesis of human type 1 diabetes as well as in its model non-obese diabetic (NOD) mice during the perinatal period, as endogenous viruses and/or as infectious agents vertically transmitted from mothers. However, the role of virus as genetic or environmental factor and its interaction with other maternal factors remain unclear. In a series of experiments, we transplanted preimplantation-stage NOD embryos into the uterus of recipient Institute of Cancer Research (ICR) mice, which are without diabetic genetic predisposition, and NOD mice, which did not exhibit overt diabetes during the experiment, and designated offspring as NOD/ICR and NOD/NOD, respectively. We previously observed that NOD/ICR offspring developed insulitis significantly earlier than NOD/NOD offspring. To assess the role of viruses in the development of insulitis, we examined the appearance of viral particles and expression of retroviruses between NOD/ICR and NOD/NOD. NOD/ICR showed earlier expression of env region of the xenotropic type C retrovirus by polymerase chain reaction analysis than NOD/NOD, while the retrovirus-like particles were observed in the islet b-cells similarly in both groups by electron microscopy. Serum corticosterone level, which is suggested to enhance retroviral induction, was significantly higher in the ICR than in the NOD surrogate mothers. These findings suggest that the observed virus is endogenous and that maternal environmental factors, including hormone levels, affect the induction of endogenous viruses and cause the earlier onset of insulitis. [source] Evaluation of Right Ventricular Fibrosis in Adult Congenital Heart Disease Using Gadolinium-enhanced Magnetic Resonance Imaging: Initial Experience in Patients with Right Ventricular Loading ConditionsCONGENITAL HEART DISEASE, Issue 5 2006Lopa P. Hartke MD ABSTRACT Objective., Gadolinium-enhanced cardiac magnetic resonance imaging has been used to show myocardial fibrosis, a finding that appears as late gadolinium enhancement. Its role in the evaluation of right ventricular fibrosis in congenital heart disease is unclear. The purpose of this study was to demonstrate late gadolinium enhancement of the right ventricle in adult and adolescent congenital heart disease and to investigate the relationship between this enhancement and clinical and pathophysiological data. Design., In total, 24 patients, 16 patients with congenital heart disease and right ventricular loading conditions and 8 controls, underwent gadolinium-enhanced viability imaging. Diagnoses varied and included repaired, palliated, and unrepaired lesions. The presence and extent of right ventricular late gadolinium enhancement was compared with patient clinical and hemodynamic data. Exact Wilcoxon tests, Fisher's exact tests, and Spearman's rank correlation were used to compare variables. Results., Nine of 16 patients (56%) were found to have right ventricular late gadolinium enhancement, ranging from 5% to 80% of right ventricular myocardium affected (mean 36.1%, SD 29.7). The combination of right ventricular systolic pressure ,98 mm Hg and systemic oxygen saturation ,93% strongly suggested the presence of right ventricular late gadolinium enhancement (positive predictive value 100%), but no single variable or combination of variables could reliably predict its absence (negative predictive values ,75%). Extent of right ventricular late gadolinium enhancement did not correlate with degree of either hypoxia or right ventricular hypertension. Conclusions., Gadolinium-enhanced cardiac magnetic resonance demonstrates right ventricular late gadolinium enhancement in some patients with congenital heart disease and right ventricular loading conditions. Clinical variables were associated with the presence of fibrosis but did not reliably predict severity. Myocardial preservation is likely a multifactorial process that may affect the right and left ventricles differently. [source] Racial and Gender Trends in the Use of Implantable Cardioverter-Defibrillators Among Medicare Beneficiaries Between 1997 and 2003CONGESTIVE HEART FAILURE, Issue 2 2009Paul S. Chan MD Differences in the use of implantable cardioverter-defibrillators (ICDs) have been reported, but the extent to which they have widened after the publication of major clinical trials supporting their use is unclear. Using data on Medicare beneficiaries, the authors determined annual age-standardized population-based utilization rates of ICDs for white men, black men, white women, and black women from 1997 to 2003. During the study period, overall use of ICDs increased most for white men (81.7,254.7 procedures per 100,000 from 1997 to 2003) and black men (38.0,151.7 procedures per 100,000), with white women (28.9,98.4 procedures per 100,000) and black women (18.2,77.3 procedures per 100,000) showing smaller increases in comparison. After adjustment with multivariable regression models, differences in utilization rates between whites and men widened compared with blacks and women between 1997 and 2003, a period when indications for ICD therapy have expanded. [source] Dynamic Analysis of Exercise Oxygen Consumption Predicts Outcomes in Advanced Heart FailureCONGESTIVE HEART FAILURE, Issue 6 2007Guy A. MacGowan MD It is unclear whether cardiopulmonary stress testing provides prognostic information in patients with very advanced heart failure receiving contemporary medical therapy. Analysis of cardiopulmonary treadmill stress data in a group of patients with advanced heart failure and severe functional impairment was performed (N=102, peak exercise oxygen consumption [VO2] ,14 mL/kg/min, 47% receiving ,-blockers). Dynamic variables (peak - baseline values) better predicted outcomes than did single value peak measurements, especially ,VO2. Multivariate analysis showed that usage of ,-blockers and ,VO2 (both P<.05) independently and significantly predicted outcomes. Subgroup analysis showed that ,VO2 was particularly useful in predicting outcomes in patients with ischemic cardiomyopathy or who were not receiving ,-blockers. Thus, in patients with very advanced heart failure, cardiopulmonary stress testing-derived ,VO2 provides important prognostic information useful to help predict clinical deterioration or death, particularly for patients with ischemic cardiomyopathy or who are not receiving ,-blockers. [source] Loop Diuretic Therapy, Thiamine Balance, and Heart FailureCONGESTIVE HEART FAILURE, Issue 4 2007Domenic A. Sica MD Thiamine, or vitamin B1, is a water-soluble B complex vitamin that was first discovered in 1910 in the process of exploring how rice bran cured patients of beriberi. Thiamine is not synthesized in humans, therefore its availability for necessary cellular processes hinges on its continual ingestion. The amount of thiamine one needs to ingest to maintain balance is disease state-dependent or medication-dependent. Severe chronic thiamine deficiency can have significant neurologic and cardiac effects, the latter is reflected in a particular type of heart failure called wet beriberi. This form of heart failure clearly benefits from thiamine supplementation. It is unclear, however, whether thiamine supplementation offers any benefit in other forms of heart failure. Despite this, it is not unreasonable for heart failure patients to routinely ingest a thiamine-containing multivitamin; patients using diuretics have an increased urinary excretion of thiamine and thus are at a higher risk for developing thiamine deficiency. The role of thiamine in heart failure, however, remains arguable. [source] Elevated Serum Cardiac Markers Predict Coronary Artery Disease in Patients With a History of Heart Failure Who Present With Chest Pain: Insights From the i*trACS RegistryCONGESTIVE HEART FAILURE, Issue 3 2007Jonathan Glauser MD The significance of a history of heart failure (HF) in patients presenting with acute coronary syndromes and elevated cardiac markers is unclear. The authors performed an analysis of patients enrolled in the Internet Tracking Registry of Acute Coronary Syndromes (i*trACS). Cardiac marker measurement and cardiac catheterization were performed in 1174 patients. Of these, 116 (9.9%) had heart failure (HF). Coronary artery disease (CAD) was found in 61 (52.6%) patients in the HF group and 581 (54.9%) in the group without HF. In the non-HF cohort, positive markers occurred in 306 patients, in whom 217 (70.9%) had CAD at catheterization. In the HF subset, 24 patients had positive biomarkers and 15 (62.5%) had CAD. A history of HF did not lessen the likelihood of CAD as evidenced by angiography and does not diminish the utility of cardiac markers in diagnosing acute coronary syndromes. [source] Myocardial Perfusion As Assessed by Positron Emission Tomography During Long-Term Mechanical Circulatory SupportCONGESTIVE HEART FAILURE, Issue 2 2006George V. Letsou MD Although mechanical circulatory support (MCS) can improve myocardial function in patients with advanced heart failure, its effects on relative myocardial perfusion are unclear. Using positron emission tomographic imaging techniques, the authors assessed relative myocardial perfusion in patients with ischemic or idiopathic cardiomyopathy who were receiving chronic MCS with a left ventricular assist device (pulsatile HeartMate [n=2] [Thoratec Corporation, Pleasanton, CA] or nonpulsatile Jarvik 2000 [n=4] [Jarvik Heart, Inc., New York, NY]). Relative myocardial perfusion was compared at lower and higher levels of MCS (50 vs. 100,110 ejections/min for the HeartMate and 8000 vs. 12,000 rpm for the Jarvik 2000). The size and severity of perfusion defects at rest and after dipyridamole stress were measured objectively and subjectively by computer algorithms and visual inspection, respectively. Relative myocardial perfusion increased >5% from baseline in only one of six patients when MCS was increased. No change in relative myocardial perfusion of >5% was seen in any of the other five patients, even after subsequent dipyridamole stress positron emission tomographic imaging. These pilot study findings suggest that the decreased metabolic requirements induced by ventricular unloading correspondingly decreased blood flow requirements to physiologically inactive myocardium. [source] Effect of reduced total blood volume on left ventricular volumes and kinetics in type 2 diabetesACTA PHYSIOLOGICA, Issue 1 2010S. Lalande Abstract Aim:, Although impaired left ventricular (LV) diastolic function is commonly observed in patients with type 2 diabetes, it remains unclear whether the impairment is caused by altered LV relaxation or changes in LV preload. The purpose of this study was to examine the influence of LV function and LV loading conditions on stroke volume in men with type 2 diabetes. Methods:, Cardiac magnetic resonance imaging scans were performed in eight men with type 2 diabetes and 11 non-diabetic men matched for age, weight and physical activity level. Total blood volume was determined with the Evans blue dye dilution technique. Results:, End-diastolic volume (EDV), the ratio of peak early to late mitral inflow velocity (E/A) and stroke volume were lower in men with type 2 diabetes than in non-diabetic individuals. Peak filling rate and peak ejection rate were not different between diabetic and non-diabetic individuals; however, men with type 2 diabetes had proportionally longer systolic duration than non-diabetic individuals. Heart rate was higher and total blood volume was lower in men with type 2 diabetes. The lower total blood volume was correlated with a lower EDV in men with type 2 diabetes. Conclusions:, Men with type 2 diabetes have an altered cardiac cycle and lower end-diastolic and stroke volume. A lower total blood volume and higher heart rate in men with type 2 diabetes suggest that changes in LV preload, independent of changes in LV relaxation or contractility, influence LV diastolic filling and stroke volume in this population. [source] Using Population Count Data to Assess the Effects of Changing River Flow on an Endangered Riparian PlantCONSERVATION BIOLOGY, Issue 4 2006DIANE M. THOMSON análisis de viabilidad poblacional; gestión ribereña; método de difusión; presas; riesgo de extinción Abstract:,Methods for using simple population count data to project extinction risk have been the focus of much recent theoretical work, but few researchers have used these approaches to address management questions. We analyzed 15 years of census data on the federally endangered endemic riparian plant Pityopsis ruthii (Small) with the diffusion approximation (DA). Our goals were to evaluate relative extinction risk among populations in two different watersheds (in Tennessee, U.S.A.) and potential effects of variation in managed river flow on population dynamics. Populations in both watersheds had high projected risks of extinction within 50 years, but the causes of this risk differed. Populations of P. ruthii on the Hiwassee River had higher initial population sizes but significantly lower average growth rates than those on the Ocoee River. The only populations with low predicted short-term extinction risk were on the Ocoee. Growth rates for populations on both rivers were significantly reduced during periods of lower river flow. We found only marginal evidence of a quadratic relationship between population performance and flow. These patterns are consistent with the idea that low flows affect P. ruthii due to growth of competing vegetation, but the degree to which very high flows may reduce population growth is still unclear. Simulations indicated that populations were most sensitive to growth rates in low-flow years, but small changes in the frequency of these periods did not strongly increase risk for most populations. Consistent with results of other studies, DA estimates of extinction risk had wide confidence limits. Still, our results yielded several valuable insights, including the need for greater monitoring of populations on the Hiwassee and the importance of low-flow years to population growth. Our work illustrates the potential value of simple methods for analyzing count data despite the challenges posed by uncertainty in estimates of extinction risk. Resumen:,Los métodos que utilizan datos de conteos simples de la población para proyectar el riesgo de extinción han sido el foco reciente de mucho trabajo teórico, pero pocos investigadores han utilizado estos métodos para responder preguntas de gestión. Analizamos 15 años de datos de censos de la planta ribereña, endémica y federalmente en peligro Pityopsis ruthii (Small) mediante el método de difusión. Nuestras metas fueron evaluar el riesgo de extinción de poblaciones en dos cuencas hidrológicas distintas y con dos efectos potenciales de la variación del flujo de agua sobre la dinámica de la población. Las poblaciones en ambas cuencas tenían alto riesgo de extinción proyectado a 50 años, pero las causas de este riesgo difirieron. Las poblaciones de P. ruthii en el Río Hiwassee tuvieron poblaciones iniciales más grandes, pero tasas de crecimiento significativamente menores, que las poblaciones en el Río Ocoee. Las únicas poblaciones con bajo riesgo de extinción pronosticado estaban en el Ocoee. Las tasas de crecimiento de las poblaciones en ambos ríos se redujeron significativamente durante períodos de bajo flujo en el río. Sólo encontramos evidencia marginal de la relación cuadrática entre el funcionamiento de la población y el flujo. Estos patrones son consistentes con la idea de que los bajos flujos afectan a P. ruthii debido al crecimiento de vegetación competitiva, pero aun no es claro el grado en que flujos muy grandes pueden reducir el crecimiento poblacional. Las simulaciones indicaron que las poblaciones son más sensibles a las tasas de crecimiento en años con bajo flujo en los ríos, pero pequeños cambios en la frecuencia de esos períodos no aumentaron el riesgo en la mayoría de las poblaciones. Consistentemente con los resultados de otros estudios, las estimaciones del riesgo de extinción mediante el método de difusión tienen amplios límites de confianza. Aun así, nuestros resultados aportaron varios conocimientos valiosos, incluyendo la necesidad de mayor monitoreo de las poblaciones en el Hiwassee y la importancia para el crecimiento poblacional de los años con bajo flujo. Nuestro trabajo ilustra el valor potencial de métodos sencillos de análisis de datos de conteo a pesar de los retos impuestos por la incertidumbre en las estimaciones del riesgo de extinción. [source] Recreational Portage Trails as Corridors Facilitating Non-Native Plant Invasions of the Boundary Waters Canoe Area Wilderness (U.S.A.)CONSERVATION BIOLOGY, Issue 5 2005SARA JO M. DICKENS corredores; invasiones; perturbación humana; recreación; senderos Abstract:,Wilderness areas are protected and valued in part for recreation; recreational use, however, can negatively impact these areas. In particular, recreational use can facilitate transport of non-native propagules and create open sites for establishment of non-native species. We examined the role of recreational portage trails in the introduction and establishment of non-native plants into the Boundary Waters Canoe Area Wilderness of northern Minnesota (U.S.A.). On 20 portages, we sampled non-native plant richness and cover at four distances (0, 10, 25, and 50 m) from trails. Non-native richness and cover were not related to distance from wilderness entry point. Non-native richness and cover were, however, negatively related to distance from trails. All six non-native species we observed were either directly on or within 1 m of trails. These results suggest that recreational trails act as corridors facilitating invasions of non-native plants into wilderness areas. It remains unclear, however, whether these effects are caused by dispersal of propagules, creation of bare ground, or changes in the native plant community. Resumen:,En parte, las áreas silvestres son protegidas y valoradas para recreación; sin embargo, el uso recreativo puede impactar a estas áreas negativamente. En particular, el uso recreativo puede facilitar el transporte de propágulos no nativos y crear áreas abiertas para el establecimiento de especies no nativas. Examinamos el papel de senderos recreativos en la introducción y establecimiento de plantas no nativas en el Boundary Waters Canoe Area Wilderness en el norte de Minnesota (E.U.A.). En 20 senderos, muestreamos la riqueza y cobertura de plantas no nativas a cuatro distancias (0, 10, 25 y 50 m) de los senderos. La riqueza y cobertura de no nativas no se relacionaron con la distancia al punto de entrada al área silvestre. Sin embargo, la riqueza y cobertura de no nativas se relacionaron negativamente con la distancia a los senderos. Las seis especies no nativas fueron observadas directamente sobre o a 1 m de los senderos. Estos resultados sugieren que los senderos recreativos fungen como corredores que facilitan la invasión de plantas no nativas a las áreas silvestres. Sin embargo, aún no es claro si estos efectos son causados por la dispersión de propágulos, la creación de suelo desnudo o por cambios en la comunidad de plantas nativas. [source] Orexins (hypocretins) actions on the GHRH/somatostatin-GH axisACTA PHYSIOLOGICA, Issue 3 2010M. López Abstract The secretion of growth hormone (GH) is regulated through a complex neuroendocrine control system that includes two major hypothalamic regulators, namely GH-releasing hormone (GHRH) and somatostatin (SST) that stimulate and inhibit, respectively, GH release. Classical experiments involving damage and electrical stimulation suggested that the lateral hypothalamic area (LHA) modulated the somatotropic axis, but the responsible molecular mechanisms were unclear. Evidence obtained during the last decade has demonstrated that orexins/hypocretins, a family of peptides expressed in the LHA controlling feeding and sleep, play an important regulatory role on GH, by inhibiting its secretion modulating GHRH and SST neurones. Considering that GH release is closely linked to the sleep,wake cycle and feeding state, understanding orexin/hypocretin physiology could open new therapeutic possibilities in the treatment of sleep, energy homeostasis and GH-related pathologies, such as GH deficiency. [source] Irritants in combination with a synergistic or additive effect on the skin response: an overview of tandem irritation studiesCONTACT DERMATITIS, Issue 6 2006Francisca Kartono Sodium lauryl sulfate (SLS) has often been chosen as a model for irritant contact dermatitis (ICD) to study the effect of irritants in combination (1,14). Recently ,tandem', or sequential, exposures with SLS have been performed to study the mechanism of skin barrier impairment in ICD (1,6, 15). The assessment of reactions have been documented with visual scoring, transepidermal water loss (TEWL), skin colour reflectance measurements, skin blood flow; among which TEWL has been noted as the most sensitive value (16). The matched control groups were treated with either a single exposure to a single irritant or in tandem with the same irritant repeatedly. Synergistic and additive effects have been reported for various tandem pairs of irritants, however, the mechanism for both remains unclear. The results of tandem irritation studies were evaluated to define and investigate the responses produced and deduce a possible mechanism of action. Clinical ramifications, albeit complex, are discussed. [source] Forearm and leg amino acid metabolism in the basal state and during combined insulin and amino acid stimulation after a 3-day fastACTA PHYSIOLOGICA, Issue 3 2009J. Gjedsted Abstract Aim:, Fasting is characterized by a progressive loss of protein, but data on protein kinetics are unclear and few have studied the effects of re-feeding. The present study was designed to test the hypothesis that a combined infusion of insulin and amino acids after fasting would induce compensatory increases in protein synthesis and reductions in protein breakdown at the whole body level and in muscle. Methods:, We included 10 healthy male volunteers and studied them twice: (1) in the post-absorptive state and (2) after 72 h of fasting. Amino acid kinetics was measured using labelled phenylalanine and tyrosine, whole body energy expenditure was assessed and urea nitrogen synthesis rates were calculated. Results:, After fasting we observed an increase in arterial blood concentration of branched chain amino acids and a decrease in gluconeogenic amino acids (P < 0.05). Isotopically determined whole body, forearm and leg phenylalanine fluxes were unaltered apart from a 30% decrease in phenylalanine-to-tyrosine conversion (2.0 vs. 1.4 ,mol kg,1 h,1, P < 0.01). During infusion of insulin and amino acids, amino acid concentrations increased. Conclusion:, Our data indicate that after a 72-h fast basal and insulin/amino acid-stimulated regional phenylalanine fluxes in leg and forearm muscle are unaltered. During fasting concentrations of gluconeogenic amino acids decrease and hepatic and/or renal phenylalanine-to-tyrosine conversion decreases. Thus, as opposed to glucose and lipid metabolism, fasting does not induce insulin resistance as regards amino acid metabolism. [source] DHEA improves impaired activation of Akt and PKC ,/,-GLUT4 pathway in skeletal muscle and improves hyperglycaemia in streptozotocin-induced diabetes ratsACTA PHYSIOLOGICA, Issue 3 2009K. Sato Abstract Aim:, Addition of dehydroepiandrosterone (DHEA) to a cultured skeletal muscle locally synthesizes 5,-dihydrotestosterone (DHT). It induced activation of glucose metabolism-related signalling pathway via protein kinase B (Akt) and protein kinase C zeta/lambda (PKC ,/,)-glucose transporter-4 (GLUT4) proteins. However, such an effect of DHEA in vivo remains unclear. Methods:, Using streptozotocin (STZ)-induced rats with type 1 diabetes mellitus, we tested the hypothesis that a single bout of DHEA injection in the rats improves hyperglycaemia and muscle GLUT4-regulated signalling pathway. After 1 week of STZ injection (55 mg kg,1) with male Wistar rats, fasting glucose concentrations were determined in a blood sample taken from the tail vein. Blood glucose levels were then monitored for 180 min after DHEA or sesame oil (control) was injected (n = 10 for each group). Results:, Blood glucose levels decreased significantly for 30,150 min after 2 mg DHEA injection in the STZ rats. In the skeletal muscle, expression and translocation of GLUT4 protein, phosphorylation of Akt and PKC ,/,, and phosphofructokinase and hexokinase enzyme activities increased significantly by DHEA injection. However, DHEA-induced improvements in Akt and PKC ,/,-GLUT4 pathways were blocked by a DHT inhibitor. Conclusion:, These results suggest that a single bout of DHEA injection can improve hyperglycaemia and activate the glucose metabolism-related signalling pathway via Akt and PKC ,/,-GLUT4 proteins of skeletal muscles in rats. Moreover, these results show that a DHEA-induced increase in muscle glucose uptake and utilization might contribute to improvement in hyperglycaemia in type 1 diabetes mellitus. [source] The role of inhibitory neurotransmission in locomotor circuits of the developing mammalian spinal cordACTA PHYSIOLOGICA, Issue 2 2009H. Nishimaru Abstract Neuronal circuits generating the basic coordinated limb movements during walking of terrestrial mammals are localized in the spinal cord. In these neuronal circuits, called central pattern generators (CPGs), inhibitory synaptic transmission plays a crucial part. Inhibitory synaptic transmission mediated by glycine and GABA is thought to be essential in coordinated activation of muscles during locomotion, in particular, controlling temporal and spatial activation patterns of muscles of each joint of each limb on the left and right side of the body. Inhibition is involved in other aspects of locomotion such as control of speed and stability of the rhythm. However, the precise roles of neurotransmitters and their receptors mediating inhibitory synaptic transmission in mammalian spinal CPGs remain unclear. Moreover, many of the inhibitory interneurones essential for output pattern of the CPG are yet to be identified. In this review, recent advances on these issues, mainly from studies in the developing rodent spinal cord utilizing electrophysiology, molecular and genetic approaches are discussed. [source] The effect of strength training on the force of twitches evoked by corticospinal stimulation in humansACTA PHYSIOLOGICA, Issue 2 2009T. J. Carroll Abstract Aim:, Although there is considerable evidence that strength training causes adaptations in the central nervous system, many details remain unclear. Here we studied neuromuscular responses to strength training of the wrist by recording electromyographic and twitch responses to transcranial magnetic stimulation (TMS) and cervicomedullary stimulation of the corticospinal tract. Methods:, Seventeen participants performed 4 weeks (12 sessions) of strength training for the radial deviator (RD) muscles of the wrist (n = 8) or control training without external load (n = 9). TMS recruitment curves were constructed from stimuli at five to eight intensities ranging between 15% below resting motor threshold and maximal stimulator output, both at rest and during isometric wrist extension (EXT) and RD at 10% and 50% of maximal voluntary contraction (MVC). Responses to weak TMS and cervicomedullary stimulation (set to produce a response of 10% maximal M wave amplitude during 10% MVC EXT contraction) were also compared at contraction strengths ranging from 10% to 75% MVC. Results:, Isometric strength increased following strength training (10.7% for the RD MVC, 8.8% for the EXT MVC), but not control training. Strength training also significantly increased the amplitude of TMS- and cervicomedullary-evoked twitches during low-force contractions. Increases in the force-generating capacity of the wrist extensor muscles are unlikely to account for this finding because training did not affect the amplitude of twitches elicited by supra-maximal nerve stimulation. Conclusion:, The data suggest that strength training induces adaptations that increase the net gain of corticospinal-motor neuronal projections to the trained muscles. [source] Board Monitoring, Regulation, and Performance in the Banking Industry: Evidence from the Market for Corporate ControlCORPORATE GOVERNANCE, Issue 5 2010Jens Hagendorff ABSTRACT Manuscript Type: Empirical Research Question/Issue: The specific monitoring effect of boards of directors versus industry regulation is unclear. In this paper, we examine how the interaction between bank-level monitoring and regulatory regimes influences the announcement period returns of acquiring banks in the US and twelve European economies. Research Findings/Insights: We study three board monitoring mechanisms , independence, CEO-chair duality, and diversity , and analyze their effectiveness in preventing underperforming merger strategies under bank regulators of varying strictness. Only under strict banking regulation regimes, do board independence and diversity improve acquisition performance. In less strict regulatory environments, corporate governance is virtually irrelevant in improving the performance outcomes of merger activities. Theoretical/Academic Implications: Our results indicate a complementary role between monitoring by boards and bank regulation. This study is the first to report evidence consistent with complementarity by investigating the effectiveness (rather than the prevalence) of governance arrangements across regulatory regimes. Practitioner/Policy Implications: Our work offers insights to policymakers charged with improving the quality of decision-making at financial institutions. Attempts to improve the ability of bank boards to critically assess managerial initiatives are most likely to be successful if internal governance is accompanied by strict industry regulation. [source] Corporate Governance and Financial Distress: evidence from TaiwanCORPORATE GOVERNANCE, Issue 3 2004Tsun-Siou Lee Prior empirical evidence supports the wealth expropriation hypothesis that weak corporate governance induced by certain types of ownership structures and board composition tends to result in minority interest expropriation. This in turn reduces corporate value. However, it is still unclear whether corporate financial distress is related to these corporate governance characteristics. To answer this question, we adopt three variables to proxy for corporate governance risk, namely, the percentage of directors occupied by the controlling shareholder, the percentage the controlling shareholders shareholding pledged for bank loans (pledge ratio), and the deviation in control away from the cash flow rights. Binary logistic regressions are then fitted to generate dichotomous prediction models. Taiwanese listed firms, characterised by a high degree of ownership concentration, similar to that in most countries, are used as our empirical samples. The evidence suggests that the three variables mentioned above are positively related to the risk for financial distress in the following year. Generally speaking, firms with weak corporate governance are vulnerable to economic downturns and the probability of falling into financial distress increases. [source] Making sense of CSR communicationCORPORATE SOCIAL RESPONSIBILITY AND ENVIRONMENTAL MANAGEMENT, Issue 3 2009Paul Ziek Abstract Although a great deal of research has focused on communicating Corporate Social Responsibility (CSR), the literature is diverse and encompasses a plethora of theories and approaches. It is still unclear what communicative behaviors carry the messages of organizational virtuosity and the implementation of responsible initiatives. What is missing is a simple, inclusive assessment of how organizations explicitly communicate the behaviors that constitute CSR. Accordingly, the purpose of this paper is to provide an illustration of the accounts that constitute CSR communication. Fifty US firms are examined for CSR moves within a variety of organizational contexts. The results show that communicating CSR is limited to large organizations and primarily, that they communicate CSR by conveying information about classically accepted responsible and virtuous behaviors. This patterned communicative behavior is a process that organizations engage in to make sense of CSR. Copyright © 2009 John Wiley & Sons, Ltd and ERP Environment. [source] Imidazoline-induced amplification of glucose- and carbachol-stimulated insulin release includes a marked suppression of islet nitric oxide generation in the mouseACTA PHYSIOLOGICA, Issue 3 2009S. Meidute-Abaraviciene Abstract Aim:, The role of islet nitric oxide (NO) production in insulin-releasing mechanisms is unclear. We examined whether the beneficial effects of the imidazoline derivative RX 871024 (RX) on ,-cell function might be related to perturbations of islet NO production. Methods:, Experiments were performed with isolated islets or intact mice challenged with glucose or carbachol with or without RX treatment. Insulin was determined with radioimmunoassay, NO generation with high-performance liquid chromatography and expression of inducible NO synthase (iNOS) with confocal microscopy. Results:, RX treatment, in doses lacking effects on basal insulin, greatly amplified insulin release stimulated by the NO-generating secretagogues glucose and carbachol both in vitro and in vivo. RX also improved the glucose tolerance curve. Islets incubated at high glucose levels (20 mmol L,1) displayed increased NO production derived from both neuronal constitutive NO synthase (ncNOS) and iNOS. RX abrogated this glucose-induced NO production concomitant with amplification of insulin release. Confocal microscopy revealed abundant iNOS expression in , cells after incubation of islets at high but not low glucose levels. This was abolished after RX treatment. Similarly, islets cultured for 24 h at high glucose levels showed intense iNOS expression in , cells. This was abrogated with RX and followed by an amplified glucose-induced insulin release. Conclusion:, RX effectively counteracts the negative impact of ,-cell NO generation on insulin release stimulated by glucose and carbachol suggesting imidazoline compounds by virtue of NOS inhibitory properties being of potential therapeutic value for treatment of ,-cell dysfunction in hyperglycaemia and type 2 diabetes. [source] Prevalence and correlates of traumatic brain injury among delinquent youthsCRIMINAL BEHAVIOUR AND MENTAL HEALTH, Issue 4 2008Brian E. Perron Background,Delinquent youth frequently exhibit high-risk behaviours that can result in serious injury. However, little is known about traumatic brain injuries (TBIs) and their correlates in this population. Aims,To examine the period prevalence and correlates of TBIs in delinquent youths. Method,Interviews were conducted with 720 (97.3%) residents of 27 Missouri Division of Youth Services rehabilitation facilities between March 1 and May 31, 2003. Participants [mean age (Mage) = 15.5, standard deviation (SD) = 1.2, 87% male] completed measures assessing TBI, substance use, psychiatric symptoms, and antisocial traits/behaviours. TBI was defined as ever having sustained a head injury causing unconsciousness for more than 20 minutes. Results,Nearly one-in-five youths (18.3%) reported a lifetime TBI. Youths with TBIs were significantly more likely than youths without to be male, have received a psychiatric diagnosis, report an earlier onset of criminal behaviour/substance use and more lifetime substance use problems and past-year criminal acts, evidence psychiatric symptoms, report lifetime suicidality, be impulsive, fearless, and external in locus of control and criminally victimized in the year preceding incarceration. Male gender and frequency of own criminal victimization were important predictors of TBI in multivariate analyses. Regression analyses adjusted for demographic factors, indicated that youths with TBIs were at significantly elevated risk for current depressive/anxious symptoms, antisocial behaviour, and substance abuse problems. Conclusions,TBI is common among delinquent youth and associated with wide ranging psychiatric dysfunction; however, the causal role of TBIs in the pathogenesis of co-morbid conditions remains unclear. Copyright © 2008 John Wiley & Sons, Ltd. [source] Mechanisms of metabotropic glutamate receptor-mediated synaptic signalling in cerebellar Purkinje cellsACTA PHYSIOLOGICA, Issue 1 2009J. Hartmann Abstract The metabotropic glutamate receptors type 1 (mGluR1s) are required for a normal function of the mammalian cerebellum. These G-protein-coupled receptors are abundantly expressed in the principle cerebellar cells, namely the Purkinje neurones. Under physiological conditions, mGluR1s are activated during repetitive activity of both afferent glutamatergic synaptic inputs provided by the climbing and parallel fibres respectively. Unlike the common ionotropic glutamate receptors that underlie rapid synaptic excitation, mGluR1s produce a complex post-synaptic response consisting of a Ca2+ -release signal from intracellular stores and a slow excitatory post-synaptic potential. While it is well established that the mGluR1-dependent Ca2+ -release signal from intracellular stores involves the activation of inositol-trisphosphate receptors, the mechanisms underlying the slow synaptic excitation remained unclear. Here we will review recent evidence indicating an essential role of C-type transient receptor potential (TRPC) cation channels, especially that of the subunit TRPC3, for the generation of the mGluR1-dependent synaptic current. For the signalling pathways underlying both, Ca2+ -release from intracellular stores and the slow synaptic potential, we present current knowledge about the activators, downstream effectors and possible roles for mGluR1-dependent signalling in Purkinje neurones. [source] DISRUPTING ILLEGAL FIREARMS MARKETS IN BOSTON: THE EFFECTS OF OPERATION CEASEFIRE ON THE SUPPLY OF NEW HANDGUNS TO CRIMINALS,CRIMINOLOGY AND PUBLIC POLICY, Issue 4 2005ANTHONY A. BRAGA Research Summary: The question of whether the illegal firearms market serving criminals and juveniles can be disrupted has been vigorously debated in policy circles and in the literature on firearms and violence. To the extent that prohibited persons, in particular, are supplied with guns through systematic gun trafficking, focused regulatory and investigative resources may be useful in disrupting the illegal supply of firearms to criminals. In Boston, a gun market disruption strategy was implemented that focused on shutting down illegal diversions of new handguns from retail sources. Multivariate regression analyses were used to estimate the effects of the intervention on new handguns recovered in crime. Our results suggest that focused enforcement efforts, guided by strategic analyses of ATF firearms trace data, can have significant impacts on the illegal supply of new handguns to criminals. Policy Implications: The problem-oriented policing approach provides an appropriate framework to uncover the complex mechanisms at play in illicit firearms markets and to develop tailor-made interventions to disrupt the illegal gun trade. Strategic enforcement programs focused on the illegal diversion of new firearms from primary markets can reduce the availability of new guns to criminals. However, the extent to which criminals substitute older guns for new guns and move from primary markets to secondary markets in response to an enforcement strategy focused on retail outlets remains unclear. Our evaluation also does not provide policy makers with any firm evidence on whether supply-side enforcement strategies have any measurable impacts on gun violence. Jurisdictions suffering from gun violence problems should implement demand-side violence prevention programs to complement their supply-side efforts. [source] Peripheral blood MDS score: A new flow cytometric tool for the diagnosis of myelodysplastic syndromes,CYTOMETRY, Issue 1 2005Sindhu Cherian Abstract Background Myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic disorders diagnosed using morphologic and clinical findings supported by cytogenetics. Because abnormalities may be subtle, diagnosis using these approaches can be challenging. Flow cytometric (FCM) approaches have been described; however the value of bone marrow immunophenotyping in MDS remains unclear due to the variability in detected abnormalities. We sought to refine the FCM approach by using peripheral blood (PB) to create a clinically useful tool for the diagnosis of MDS. Methods PB from 15 patients with MDS was analyzed by multiparametric flow cytometry using an extensive panel of monoclonal antibodies. Patterns of neutrophil antigen expression were compared with those of normal controls (n = 16) to establish light scatter and/or immunophenotypic abnormalities that correlated with MDS. A scoring algorithm was developed and validated prospectively on a blinded patient set. Results PB neutrophils from patients with MDS had lower side scatter and higher expression of CD66 and CD11a than did controls. Some MDS PB neutrophils demonstrated abnormal CD116 and CD10 expression. Because none of these abnormalities proved consistently diagnostic, we sought to increase the power of the assay by devising a scoring system to allow the association of multiple abnormalities and account for phenotypic variations. The PB MDS score differentiated patients with MDS from controls (P < 0.0001) in the test set. In a prospective validation, the PB MDS score successfully identified patients with MDS (sensitivity 73%, specificity 90%). Conclusions FCM analysis of side scatter and only four additional immunophenotypic parameters of PB neutrophils using the PB MDS score proved more sensitive than standard laboratory approaches and may provide an additional, more reliable diagnostic tool in the identification of MDS. © 2005 Wiley-Liss, Inc. [source] Actin on DNA,An ancient and dynamic relationship,CYTOSKELETON, Issue 8 2010Kari-Pekka Skarp Abstract In the cytoplasm of eukaryotic cells the coordinated assembly of actin filaments drives essential cell biological processes, such as cell migration. The discovery of prokaryotic actin homologues, as well as the appreciation of the existence of nuclear actin, have expanded the scope by which the actin family is utilized in different cell types. In bacteria, actin has been implicated in DNA movement tasks, while the connection with the RNA polymerase machinery appears to exist in both prokaryotes and eukaryotes. Within the nucleus, actin has further been shown to play a role in chromatin remodeling and RNA processing, possibly acting to link these to transcription, thereby facilitating the gene expression process. The molecular mechanism by which actin exerts these newly discovered functions is still unclear, because while polymer formation seems to be required in bacteria, these species lack conventional actin-binding proteins to regulate the process. Furthermore, although the nucleus contains a plethora of actin-regulating factors, the polymerization status of actin within this compartment still remains unclear. General theme, however, seems to be actin's ability to interact with numerous binding partners. A common feature to the novel modes of actin utilization is the connection between actin and DNA, and here we aim to review the recent literature to explore how this connection is exploited in different contexts. [source] | |||||||||||||||||||||||||||||||||||||||||||