Low adiponectin is associated with increased ambulatory pulse pressure and activation of the renin-angiotensin system in subjects of African descent

Purpose: Adiponectin, arterial stiffness, as well components of the renin-angiotensin system are associated with cardiovascular risk. This study was aimed to investigate whether plasma adiponectin was directly linked with pulse pressure (PP), as a marker for arterial stiffness, and the renin-angiotensin system (RAS). Methods and materials: A family-based study in subjects of African descent enriched with hypertensive patients was carried out in the Seychelles. Fasting plasma adiponectin was determined by ELISA, plasma renin activity according to the antibody-trapping principle and plasma aldosterone by radioimmunoassay. Daytime ambulatory blood pressure (BP) was measured using Diasys Integra devices. PP was calculated as the difference between systolic and diastolic BP. The association of adiponectin with PP, plasma renin activity and plasma aldosterone were analyzed using generalized estimating equations with a gaussian family link and an exchangeable correlation structure to account for familial aggregation. Results: Data from 335 subjects from 73 families (152 men, 183 women) were available. Men and women had mean (SD) age of 45.4 ± 11.1 and 47.3 ± 12.4 years, BMI of 26.3 ± 4.4 and 27.8 ± 5.1 kg/m2, daytime systolic/diastolic BP of 132.6 ± 15.4 / 86.1 ± 10.9 and 130 ± 17.6 / 83.4 ± 11.1 mmHg, and daytime PP of 46.5 ± 9.9 and 46.7 ± 10.7 mmHg, respectively. Plasma adiponectin was 4.4± 3.04 ng/ml in men and 7.39 ± 5.44 ng/ml in women (P <0.001). After adjustment for age, sex and BMI, log-transformed adiponectin was negatively associated with daytime PP (-0.009 ± 0.003, P = 0.004), plasma renin activity (-0.248 ± 0.080, P = 0.002) and plasma aldosterone (-0.004 ± 0.002, P = 0.014). Conclusion: Low adiponectin is associated with increased ambulatory PP and RAS activation in subjects of African descent. Our data are consistent with the observation that angiotensin II receptor blockers increase adiponectin in humans.

Diffusion tensor echo planar imaging using surface coil transceiver with a semiadiabatic RF pulse sequence at 14.1T.

Diffusion magnetic resonance studies of the brain are typically performed using volume coils. Although in human brain this leads to a near optimal filling factor, studies of rodent brain must contend with the fact that only a fraction of the head volume can be ascribed to the brain. The use of surface coil as transceiver increases Signal-to-Noise Ratio (SNR), reduces radiofrequency power requirements and opens the possibility of parallel transmit schemes, likely to allow efficient acquisition schemes, of critical importance for reducing the long scan times implicated in diffusion tensor imaging. This study demonstrates the implementation of a semiadiabatic echo planar imaging sequence (echo time=40 ms, four interleaves) at 14.1T using a quadrature surface coil as transceiver. It resulted in artifact free images with excellent SNR throughout the brain. Diffusion tensor derived parameters obtained within the rat brain were in excellent agreement with reported values.

Habitat selection in zones of parapatric contact between the common shrew Sorex araneaus and Millet's shrew S. coronatus

(1) The common shrew Sorex araneus and Millet's shrew S. coronatusare sibling species.They are morphologically and genetically very similar but do not hybridize.Their parapatric distribution throughout south-western Europe, with a few narrow zones of distributional overlap, suggests that they are in competitive parapatry. (2) Two of these contact zones were studied; there was evidence of coexistence over periods of 2 years as well as habitat segregation. In both zones, the species segregated on litter thickness and humidity variables. (3) A simple analysis of spatial distribution showed that habitats visible in the field corresponded to the habitats selected by the species. Habitat selection was found throughout the annual life-cycle of the shrews. (4) In one contact zone, a removal experiment was performed to test whether habitat segregation is induced by interspecific interactions. The experiment showed that the species select habitats differentially when both are present and abandon habitat selection when their competitor removed. (5)These results confirm the role of resource partitioning in promoting narrow ranges of distributional overlap between such parapatric species and qualitatively support the prediction of habitat selection theory that, in a two-species system, coexistence may be achieved by differential habitat selection to avoid competition. The results also support the view that the common shrew and Millet's shrew are in competitive parapatry.

Hematopoietic stem cells reversibly switch from dormancy to self-renewal during homeostasis and repair.

Bone marrow hematopoietic stem cells (HSCs) are crucial to maintain lifelong production of all blood cells. Although HSCs divide infrequently, it is thought that the entire HSC pool turns over every few weeks, suggesting that HSCs regularly enter and exit cell cycle. Here, we combine flow cytometry with label-retaining assays (BrdU and histone H2B-GFP) to identify a population of dormant mouse HSCs (d-HSCs) within the lin(-)Sca1+cKit+CD150+CD48(-)CD34(-) population. Computational modeling suggests that d-HSCs divide about every 145 days, or five times per lifetime. d-HSCs harbor the vast majority of multilineage long-term self-renewal activity. While they form a silent reservoir of the most potent HSCs during homeostasis, they are efficiently activated to self-renew in response to bone marrow injury or G-CSF stimulation. After re-establishment of homeostasis, activated HSCs return to dormancy, suggesting that HSCs are not stochastically entering the cell cycle but reversibly switch from dormancy to self-renewal under conditions of hematopoietic stress.

Contribution à l'étude neuroanatomique de systèmes enzymatiques impliqués dans le métabolisme énergétique cérébral

RESUME Il a longtemps été admis que le glucose était le principal, sinon le seul substrat du métabolisme énergétique cérébral. Néanmoins, des études récentes indiquent que dans des situations particulières, d'autres substrats peuvent être employés. C'est le cas des monocarboxylates (lactate et pyruvate principalement). Bien que la barrière hématoencéphalique soit peu perméable à ces molécules, elles deviennent néanmoins des substrats possibles si elles sont produites localement. Les deux systèmes enzymatiques pivots des voies glycolytiques et oxydatives sont la lactate déshydrogénase (LDH, EC 1.1.1.27) qui catalyse l'interconversion du pyruvate et du lactate et le complexe pyruvate déshydrogénase qui catalyse la conversion irréversible du pyruvate en acétyl-CoA qui entre dans la respiration mitochondriale. Nous avons étudié la localisation, tant régionale que cellulaire, des isoformes LDH-1, LDH-5 et PDHEla dans le cerveau du chat et dé l'homme au moyen de diverses techniques histologiques. Dans un premier temps, des investigations par hybridation in situ au moyen d'oligosondes marquées au 33P sur de coupes de cerveau de chat ont permis de montrer une différence de l'expression des enzymes à vocation oxydative (LDH-1 et PDHA1, le gène codant pour la protéine PDHEIa) par rapport à LDH-5, isoforme qui catalyse préférentiellement la formation de lactate. LDH-1 et PDHA 1 ont des distributions similaires et sont enrichies dans de nombreuses structures cérébrales, comme l'hippocampe, de nombreux noyaux thalamiques et des structures pontiques. Le cortex cérébral exhibe également une expression importante de LDH-1 et PDH. LDH-5 a par contre une expression largement plus diffuse à travers le cerveau, bien que l'on trouve néanmoins un enrichissement plus important dans l'hippocampe. Ces résultats sont en accord avec les observations que nous avons précédemment publiées chez le rongeur pour LDH-1 et LDH-5 (Laughton et collaborateurs, 2000). Des analyses par PCR en temps réel ont confirmé que dans certaines régions, LDH-1 est exprimée de façon nettement plus importante que LDH-5. Dans un deuxième temps, nous avons appliqué sur des coupes histologiques d'hippocampe et de cortex occipital humain post-mortem des anticorps monoclonaux spécifiques de l'isoforme LDH-5 et la sous-unité PDHela du complexe pyruvate déshydrogénase. Là aussi, les immunoréactions révèlent une ségrégation régionale mais aussi cellulaire des deux enzymes. Dans les deux régions étudiées, LDH-5 est localisée exclusivement dans les astrocytes. Dans le cortex occipital, la matière blanche et également la couche I corticale sont immunopositives pour LDH-5. Dans l'hippocampe, le CA4 et l'alveus exhibe l'immunomarquage le plus intense pour LDH-5. Seuls des neurones (à de rares exceptions quelques astrocytes) sont immunopositifs à l'anticorps monoclonal dirigé contre PDHela. La couche IV du cortex occipital présente la plus forte immunoréaction. Dans l'hippocampe, une immunoréactivité est observée dans le stratum granulosum et à travers la région CA1 jusqu'à la région CA3. L'ensemble de ces résultats montre une hétérogénéité métabolique dans le cerveau et étaye l'hypothèse "astrocyte-neurone lactate shuttle" (ANL5) (Bittar et collaborateurs, 1996; Magistretti et Pellerin, 1999) qui propose que les astrocytes fournissent aux neurones activés du lactate comme substrat alternatif de leur métabolisme énergétique. ABSTRACT For a long time now, glucose has been thought to be the main, if not the sole substrate for brain energy metabolism. Recent data nevertheless suggest that other molecules, such as monocarboxylates (lactate and pyruvate mainly) could be suitable substrates. Although monocarboxylates poorly cross the blood brain barrier (BBB), such substrates could replace glucose if produced locally. The two key enzymatic systems required for the use and production of these substats are lactate dehydrogenase (LDH; EC 1.1.1.27) that catalyses the interconversion of lactate and pyruvate and the pyruvate dehydrogenase complex that irreversibly funnels pyruvate towards the mitochondrial TCA cycle and oxydative phosphorylation. Our study consisted in localizing these different systems with various histochemical procedures in the cat brain and two regions, i.e. hippocampus and primary visual cortex, of the human brain. First, by means of in situ hybridization with 33P labeled oligoprobes, we have demonstrated that the more oxidative enzymes (LDH-1 and PDHA1, the gene coding for PDHEla) are highly expressed in a variety of feline brain structures. These structures include the hippocampus, various thalamic nuclei and the pons. The cerebral cortex exhibits also a high LDH-1 and PDHAl expression. On the other hand, LDH-5 expression is poorer and more diffuse, although the hippocampus does seem to have a higher expression. These fmdings are consistent with our previous observation of the expression of LDH1 and LDH-5 in the rodent brain (Laughton et al, 2000). Real-time PCR (TagMan tm) revealed that, in various regions, LDH-1 is effectively more highly expressed than LDH-5. In a second set of experiments, monoclonal antibodies to LDH-5 and PDHeIa were applied to cryostat sections of post-mortem human hippocampus and occipital cortex. These procedures revealed not only that the two enzymes have different regional distributions, but also distinct cellular localisation. LDH-5 immunoreactivity is solely observed in astrocytes. In the occipital cortex, the white matter and layer I are immunopositive. In the hippocampus, the alveus and CA4 show LDH-5 immunoréactivity. PDHeIa has been detected, with few exceptions, only in neurons. Layer IV of the occipital cortex was most immmunoreactive. In the hippocampus, PDHela immunoreactivity is noticed in the stratum granulosum and through CA 1 to CA3 areas. The overall observations made in this study show that there is a metabolic heterogeneity in the brain and our findings support the hypothesis of an astrocyte-neuron lactate shuttle (ANLS)(Bittar et al., 1996; Magistretti & Pellerin, 1999) where astrocytes export to active neurons lactate to fuel their energy demands.

Inclusion of soil erosion impacts in life cycle assessment on a global scale: application to energy crops in Spain

Purpose: Despite the fundamental role of ecosystem goods and services in sustaining human activities, there is no harmonized and internationally agreed method for including them in life cycle assessment (LCA). The main goal of this study was to develop a globally applicable and spatially resolved method for assessing land-use impacts on the erosion regulation ecosystem service.Methods: Soil erosion depends much on location. Thus, unlike conventional LCA, the endpoint method was regionalized at the grid-cell level (5 arc-minutes, approximately 10×10 km2) to reflect the spatial conditions of the site. Spatially explicit characterization factors were not further aggregated at broader spatial scales. Results and discussion: Life cycle inventory data of topsoil and topsoil organic carbon (SOC) losses were interpreted at the endpoint level in terms of the ultimate damage to soil resources and ecosystem quality. Human health damages were excluded from the assessment. The method was tested on a case study of five three-year agricultural rotations, two of them with energy crops, grown in several locations in Spain. A large variation in soil and SOC losses was recorded in the inventory step, depending on climatic and edaphic conditions. The importance of using a spatially explicit model and characterization factors is shown in the case study.Conclusions and outlook: The regionalized assessment takes into account the differences in soil erosion-related environmental impacts caused by the great variability of soils. Taking this regionalized framework as the starting point, further research should focus on testing the applicability of the method trough the complete life cycle of a product and on determining an appropriate spatial scale at which to aggregate characterization factors, in order to deal with data gaps on location of processes, especially in the background system. Additional research should also focus on improving reliability of the method by quantifying and, insofar as it is possible, reducing uncertainty.

Iowa, the anniversary of her statehood, December 28 : a few books about Iowa, 1902

This leaflet includes information on books and reference materials that can found in libraries on the Statehood of Iowa.

Fluorodeoxyuridine mediated cell cycle synchronization in S-phase increases the Auger radiation cell killing with 125I-iododeoxyuridine.

Aim: 125I-iododeoxyuridine is a potential Auger radiation therapy agent. Its incorporation in DNA of proliferating cells is enhanced by fluorodeoxyuridine. Here, we evaluated therapeutic activities of 125I-iododeoxyuridine in an optimized fluorodeoxyuridine pre-treatment inducing S-phase synchronization. Methods: After S-phase synchronization by fluorodeoxyuridine, cells were treated with 125I-iododeoxyuridine. Apoptosis analysis and S-phase synchronization were studied by flow cytometry. Cell survival was determined by colony-forming assay. Based on measured growth parameters, the number of decays per cell that induced killing was extrapolated. Results: Treatment experiments showed that 72 to 91% of synchronized cells were killed after 0.8 and 8 kBq/ml 125I-iododeoxyuridine incubation, respectively. In controls, only 8 to 38% of cells were killed by corresponding 125I-iododeoxyuridine activities alone and even increasing the activity to 80 kBq/ml gave only 42 % killing. Duplicated treatment cycles or repeated fluorodeoxyuridine pre-treatment allowed enhancing cell killing to >95 % at 8 kBq/ml 125I-iododeoxyuridine. About 50 and 160 decays per S-phase cells in controls and S-phase synchronization, respectively, were responsible for the observed cell killing at 0.8 kBq/ml radio-iododeoxyuridine. Conclusion: These data show the successful application of fluorodeoxyuridine that provided increased 125I-iododeoxyuridine Auger radiation cell killing efficacy through S-phase synchronization and high DNA incorporation of radio-iododeoxyuridine.

Basic life support teaching in the second year predraduate medical curriculum: quality of acquisition after 6 months

Purpose of the study: Basic life support (BLS) and automated externaldefibrillation (AED) represent important skills to be acquired duringpregraduate medical training. Since 3 years, our medical school hasintroduced a BLS-AED course (with certification) for all second yearmedical students. Few reports about quality and persistence over timeof BLS-AED learning are available to date in the medical literature.Comprehensive evaluation of students' acquired skills was performedat the end of the 2008 academic year, 6 month after certification.Materials and methods: The students (N = 142) were evaluated duringa 9 minutes «objective structured clinical examination» (OSCE) station.Out of a standardized scenario, they had to recognize a cardiac arrestsituation and start a resuscitation process. Their performance wererecorded on a PC using an Ambuman(TM) mannequin and the AmbuCPR software kit(TM) during a minimum of 8 cycles (30 compressions:2 ventilations each). BLS parameters were systematically checked. Nostudent-rater interactions were allowed during the whole evaluation.Results: Response of the victim was checked by 99% of the students(N = 140), 96% (N = 136) called for an ambulance and/or an AED. Openthe airway and check breathing were done by 96% (N = 137), 92% (N =132) gave 2 rescue breaths. Pulse was checked by 95% (N=135), 100%(N = 142) begun chest compression, 96% (N = 136) within 1 minute.Chest compression rate was 101 ± 18 per minute (mean ± SD), depthcompression 43 ± 8 mm, 97% (N = 138) respected a compressionventilationratio of 30:2.Conclusions: Quality of BLS skills acquisition is maintained during a6-month period after a BLS-AED certification. Main targets of 2005 AHAguidelines were well respected. This analysis represents one of thelargest evaluations of specific BLS teaching efficiency reported. Furtherfollow-up is needed to control the persistence of these skills during alonger time period and noteworthy at the end of the pregraduatemedical curriculum.

Passive immunization with neutralizing antibodies interrupts the mouse mammary tumor virus life cycle.

Mouse mammary tumor virus (MMTV) infects the host via mucosal surfaces and exploits the host immune system for systemic spread and chronic infection. We have tested a neutralizing rat monoclonal antibody specific for the retroviral envelope glycoprotein gp52 for its efficiency in preventing acute and chronic mucosal and systemic infection. The antibody completely inhibits the superantigen response and chronic viral infection following systemic or nasal infection. Surprisingly however, the antibody only partially inhibits the early infection of antigen-presenting cells in the draining lymph node. Despite this initially inefficient protection from infection, superantigen-specific B- and T-cell responses and systemic viral spread are abolished, leading to complete clearance of the retroviral infection and hence interruption of the viral life cycle. In conclusion, systemic neutralizing monoclonal antibodies can provide an efficient protection against chronic retroviral amplification and persistence.

Changes in Aortic Pulse Wave Velocity in Hypertension Post-Menopausal Women: Comparison Between Calcium Channel Blocker (CCB) Vs Angiotensin Receptor Blocker (ARB) Regimen

Objective: To compare effects of a non-renin-angiotensin system (RAS) blocker, using a CCB, or a RAS blocker, using an ARB regimen on the arterial stiffness reduction in postmenopausal hypertensive women. Methods: In this prospective study, a total of 125 hypertensive women (age: 61.4_6 yrs; 98% Caucasian; BW: 71.9_14 kg; BMI: 27.3_5 kg/m2; SBP/ DBP: 158_11/92_9 mmHg) were randomized between ARB (valsartan 320mg_HCTZ) and CCB (amlodipine 10mg _ HCTZ). The primary outcome was carotid-femoral pulse wave velocity (PWV) changes after 38 weeks of treatment. Results: There were no significant differences in baseline demographic data between the two groups. Both treatments effectively lowered BP at the end of the study with similar (p>0.05) reductions in the valsartan (_22.9/_10.9 mmHg) and amlodipine based (_25.2/_11.7 mmHg) treatment groups. Despite a lower (p<0.05 for DBP) central SBP/DBP in the CCB group (_19.2/_10.3 mmHg) compared to the valsartan group (_15.7/_7.6 mmHg) at week 38, a similar reduction in carotid-femoral PWV (_1.7 vs _1.9 m/sec; p>0.05) was observed between both groups. The numerically larger BP reduction observed in the CCB group was associated with a much higher incidence of peripheral edema (77% vs 14%) than the valsartan group. Conclusion: In summary, BP lowering in postmenopausal women led to a reduction in arterial stiffness assessed by PWV measurement. Both regimens reduced PWV at 38 weeks of treatment to a similar degree, despite differences in BP lowering suggesting that the effect of RAS blockade to influence PWV may partly be independent of BP.

Copeptin is not associated with menstrual cycle hormone.

Background: Copeptin (CP), a derivate from the antidiuretic hormone (ADH) precursor pre-pro-vasopressin, stochiometrically mirrors ADH secretion. CP is increasingly evaluated as a diagnostic and prognostic biomarker in different diseases. It is therefore important to recognize possible confounding factors when interpreting CP levels. In healthy regularly menstruating women, there is a small but measurable physiological variability of hormones involved in fluid regulation. ADH plasma levels have been found to be lowest at menstruation, increasing during the follicular phase with a peak at ovulation and a drop in the luteal phase. We investigated the variability of CP during the menstrual cycle (MC) and its correlation to MC hormones. Methods: In total, 15 healthy women with regular MC (from 26 to 33 days) were included in this study. Ovulation was confirmed by progesterone (prog) levels on day 21 of the MC before entering the study and during the study. Blood collection was performed on days 3, 5, 8-16, 18, 21, 24 and 27 of their MC. Serums were assayed for prog, estradiol (E2), LH, and CP. Mixed linear regression analysis for repeated measures was performed to study the changes of CP, prog, E2 and LH during the MC, and to test the correlation of CP with sex hormones during the MC. Results: Mean MC length in all subjects was 28.5±2.2 d. E2, prog, and LH exhibited characteristic changes during the MC (all P< 0.05). All cycles were ovulatory (peak prog 54±15 nmol/l). CP levels did not change significantly throughout the MC, and were not associated with changes in prog, E2 or LH-levels (all P=ns). Conclusion: CP levels remain stable during the MC and are not influenced by changes in sex hormones. This implicates that it is not necessary to consider MC phases when using CP as a biomarker in premenopausal women.

Evaluation of Maturity and Pulse Velocity Measurements for PCC Traffic Opening Decisions, HR-380, 1998

Concrete paving is often at a disadvantage in terms of pavement type selection due to the time of curing required prior to opening the pavement to traffic. The State of Iowa has been able to reduce traffic delay constraints through material selection and construction methods to date. Methods for monitoring concrete strength gain and quality have not changed since the first concrete pavements were constructed in Iowa. In 1995, Lee County and the Iowa DOT cooperated in a research project, HR-380, to construct a 7.1 mile (11. 43 km) project to evaluate the use of maturity and pulse velocity nondestructive testing (NDT) methods in the estimation of concrete strength gain. The research identified the pros and cons of each method and suggested an instructional memorandum to utilize maturity measurements to meet traffic delay demands. Maturity was used to reduce the traffic delay opening time from 5-7 days to less than 2 days through the implementation of maturity measurements and special traffic control measures. Recommendations on the development of the maturity curve for each project and the location and monitoring of the maturity thermocouples are included. Examples of equipment that could easily be used by project personnel to estimate the concrete strength using the maturity methods is described.

Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.

Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10(-8) to P = 2.3 × 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP.