Immunohistochemical and flow cytometric analysis of long-term label-retaining cells in the adult heart.

Cardiac-resident stem/progenitor cells have been identified based on expression of stem cell-associated antigens. However, no single surface marker allows to identify a definite cardiac stem/progenitor cell entity. Hence, functional stem cell markers have been extensively searched for. In homeostatic systems, stem cells divide infrequently and therefore retain DNA labels such as 5-bromo-2'-deoxyuridine, which are diluted with division. We used this method to analyze long-term label-retaining cells in the mouse heart after 14 days of 5-bromo-2'-deoxyuridine administration. Labeled cells were detected using immunohistochemical and flow-cytometric methods after varying chasing periods up to 12 months. Using mathematical models, the observed label dilution could consistently be described in the context of a 2-population model, whereby a population of rapidly dividing cells accounted for an accelerated early decline, and a population of slowly dividing cells accounted for decelerated dilution on longer time scales. Label-retaining cells were preferentially localized in the atria and apical region and stained negative for markers of the major cell lineages present in the heart. Most cells with long-term label-retention expressed stem cell antigen-1 (Sca-1). Sca-1(+)CD31(-) cells formed cell aggregates in culture, out of which lineage-negative (Lin(-))Sca-1(+)CD31(-) cells emerged, which could be cultured for many passages. These cells formed cardiospheres and showed differentiation potential into mesenchymal cell lineages. When cultured in cardiomyogenic differentiation medium, they expressed cardiac-specific genes. In conclusion, recognition of slow-cycling cells provides functional evidence of stem/progenitor cells in the heart. Lin(-)Sca-1(+)CD31(-) cardiac-derived progenitors have a potential for differentiation into cardiomyogenic and mesenchymal cell lineages.

Long-term cognitive profile and incidence of dementia after STN-DBS in Parkinson's disease

An effect of subthalamic nucleus deep brain stimulation (STN-DBS) on cognition has been suspected but long-term observations are lacking. The aim of this study was to evaluate the long-term cognitive profile and the incidence of dementia in a cohort of Parkinson's disease (PD) patients treated by STN-DBS. 57 consecutive patients were prospectively assessed by the mean of a neuropsychological battery over 3 years after surgery. Dementia (DSM-IV) and UPDRS I to IV were recorded. 24.5% of patients converted to dementia over 3 years (incidence of 89 of 1,000 per year). This group of patients cognitively continuously worsened over 3 years up to fulfilling dementia criteria (PDD). The rest of the cohort remained cognitively stable (PD) over the whole follow-up. Preoperative differences between PDD and PD included older age (69.2 +/- 5.8 years; 62.6 +/- 8 years), presence of hallucinations and poorer executive score (10.1 +/- 5.9; 5.5 +/- 4.4). The incidence of dementia over 3 years after STN-DBS is similar to the one reported in medically treated patients. The PDD presented preoperative risk factors of developing dementia similar to those described in medically treated patients. These observations suggest dementia being secondary to the natural evolution of PD rather than a direct effect of STN-DBS.

Enhancement of the photoelectrochemical properties of Cl-doped ZnO nanowires by tuning their coaxial doping profile

Arrays of vertically aligned ZnO:Cl/ZnO core-shell nanowires were used to demonstrate that the control of the coaxial doping profile in homojunction nanostructures can improve their surface charge carrier transfer while conserving potentially excellent transport properties. It is experimentally shown that the presence of a ZnO shell enhances the photoelectrochemical properties of ZnO:Cl nanowires up to a factor 5. Likewise, the ZnO shell promotes the visible photoluminescence band in highly conducting ZnO:Cl nanowires. These lines of evidence are associated with the increase of the nanowires" surface depletion layer

Activation of c-Jun in the nuclei of neurons of the CA-1 in thrombin preconditioning occurs via PAR-1.

Recently it has been shown that the c-Jun N-terminal kinase (JNK) plays a role in thrombin preconditioning (TPC) in vivo and in vitro. To investigate further the pathways involved in TPC, we performed an immunohistochemical study in hippocampal slice cultures. Here we show that the major target of JNK, the AP-1 transcription factor c-Jun, is activated by phosphorylation in the nuclei of neurons of the CA1 region by using phospho-specific antibodies against the two JNK phosphorylation sites. The activation is early and transient, peaking at 90 min and not present by 3 hr after low-dose thrombin administration. Treatment of cultures with a synthetic thrombin receptor agonist results in the same c-Jun activation profile and protection against subsequent OGD, both of which are prevented by specific JNK inhibitors, showing that thrombin signals through PAR-1 to JNK. By using an antibody against the Ser 73 phosphorylation site of c-Jun, we identify possible additional TPC substrates.

Distribution and anatomical localization of the glucose transporter 2 (GLUT2) in the adult rat brain--an immunohistochemical study.

The aim of this work was to study the distribution and cellular localization of GLUT2 in the rat brain by light and electron microscopic immunohistochemistry, whereas our ultrastructural observations will be reported in a second paper. Confirming previous results, we show that GLUT2-immunoreactive profiles are present throughout the brain, especially in the limbic areas and related nuclei, whereas they appear most concentrated in the ventral and medial regions close to the midline. Using cresyl violet counterstaining and double immunohistochemical staining for glial or neuronal markers (GFAp, CAII and NeuN), we show that two limited populations of oligodendrocytes and astrocytes cell bodies and processes are immunoreactive for GLUT2, whereas a cross-reaction with GLUT1 cannot be ruled out. In addition, we report that the nerve cell bodies clearly immunostained for GLUT2 were scarce (although numerous in the dentate gyrus granular layer in particular), whereas the periphery of numerous nerve cells appeared labeled for this transporter. The latter were clustered in the dorsal endopiriform nucleus and neighboring temporal and perirhinal cortex, in the dorsal amygdaloid region, and in the paraventricular and reuniens thalamic nuclei, whereas they were only a few in the hypothalamus. Moreover, a group of GLUT2-immunoreactive nerve cell bodies was localized in the dorsal medulla oblongata while some large multipolar nerve cell bodies peripherally labeled for GLUT2 were scattered in the caudal ventral reticular formation. This anatomical localization of GLUT2 appears characteristic and different from that reported for the neuronal transporter GLUT3 and GLUT4. Indeed, the possibility that GLUT2 may be localized in the sub-plasmalemnal region of neurones and/or in afferent nerve fibres remains to be confirmed by ultrastructural observations. Because of the neuronal localization of GLUT2, and of its distribution relatively similar to glucokinase, it may be hypothesized that this transporter is, at least partially, involved in cerebral glucose sensing.

Drug Use Profile, 2011

Historically, alcohol is the most prevalent substance of use and abuse by adults in Iowa. Research from the Behavioral Risk Factor Surveillance System compiled by the federal Centers for Disease Control and Prevention indicates that almost six of every ten adult Iowans are classified as current drinkers of alcoholic beverages. Further, one in five adult Iowans is classified as a binge drinker of alcoholic beverages, a classification indicative of abuse of, or addiction to, the substance.

Depth profile of uncompensated spins in an exchange bias system

We have used the unique spatial sensitivity of polarized neutron and soft x-ray beams in reflection geometry to measure the depth dependence of magnetization across the interface between a ferromagnet and an antiferromagnet. The net uncompensated magnetization near the interface responds to applied field, while uncompensated spins in the antiferromagnet bulk are pinned, thus providing a means to establish exchange bias.

Blood profile during and after hemoglobin substitute administration.

The in vivo effects of Diaspirin Crosslinked Hemoglobin (DCLHb, Baxter Healthcare Corp.) on hematology and biochemistry are unknown. This study includes 6 calves (71.2+/-1.3 kg). In each animal a total of 2 litres of blood was exchanged for the same amount of hydroxylethyl starch (Haes, Fresenius) (n=3) or DCLHb (n=3), which is equivalent to 28cc/kg of blood substitute, over a period of 5 hours. The animals were allowed to survive 7 days. Blood samples were taken hourly during the perfusion protocol, at postoperative day (POD) 1, 2 and 7. ANOVA test was used for repeated measurements. Blood cell profiles were similar in both groups. Peak methemoglobinemia was 4.2% in the DCLHb group. Osmolarity was significantly higher in the DCLHb group with the greatest difference at POD 1 and 2. Postmortem analysis of the major organs did not show any sign of hemoglobin deposit in the DCLHb group. In the given setup DCLHb can be administered in a large quantity with good hematological tolerance and without any deposits in major organs. A prolonged plasma expander effect was observed.

Effect of manganese chloride on the neurochemical profile of the rat hypothalamus.

Manganese (Mn(2+))-enhanced magnetic resonance imaging studies of the neuronal pathways of the hypothalamus showed that information about the regulation of food intake and energy balance circulate through specific hypothalamic nuclei. The dehydration-induced anorexia (DIA) model demonstrated to be appropriate for studying the hypothalamus with Mn(2+)-enhanced magnetic resonance imaging. Manganese is involved in the normal functioning of a variety of physiological processes and is associated with enzymes contributing to neurotransmitter synthesis and metabolism. It also induces psychiatric and motor disturbances. The molecular mechanisms by which Mn(2+) produces alterations of the hypothalamic physiological processes are not well understood. (1)H-magnetic resonance spectroscopy measurements of the rodent hypothalamus are challenging due to the distant location of the hypothalamus resulting in limited measurement sensitivity. The present study proposed to investigate the effects of Mn(2+) on the neurochemical profile of the hypothalamus in normal, DIA, and overnight fasted female rats at 14.1 T. Results provide evidence that γ-aminobutyric acid has an essential role in the maintenance of energy homeostasis in the hypothalamus but is not condition specific. On the contrary, glutamine, glutamate, and taurine appear to respond more accurately to Mn(2+) exposure. An increase in glutamine levels could also be a characteristic response of the hypothalamus to DIA.

Severely presenting strokes : profile & outcome

Etat des connaissances: Les Accidents vasculaires cérébraux (AVC) sévères sont une cause importante de mortalité et de handicap en Suisse. Les buts de cette étude sont de déterminer les caractéristiques des patients avec un AVC à présentation initiale sévère "severely presenting", ainsi que d'identifier les facteurs prédicteurs en phase aigüe et subaigüe d'un devenir favorable chez ces patients. Methodologie: En utilisant le registre des AVC "Acute STroke Registry and Analysis of Lausanne (ASTRAL), nous avons comparé tous les patients avec un AVC "à présentation sévère", defini comme un score National Institute of Health Stroke Scale (NIHSS) > 20 à l'admission aux urgences, avec tous les autres patients du registre. Dans une analyse statistique multivariée, les associations avec les caractéristiques démographiques, cliniques, pathophysiologiques, métaboliques et radiologiques des patients on été déterminées. Dans un deuxième temps, nous avons analysé les facteurs prédicteurs d'un devenir favorable à 3 mois (modified Rankin scale (mRS) <3) dans ce groupe d'AVC à présentation sévère. Resultats: Parmi les 1 '915 patients consécutifs, 243 (12.7%) présentaient un AVC rejoignant la définition de sévère. Ceux-cis étaient associés de manière significative avec un méchanisme ischémique cardio-embolique (OR=1.74 / 95% CI 1.19 - 2.54), un début inconnu de la Symptomatologie (OR=2.35 / 95% CI 1.14 - 4.83), avaient plus de trouvailles d'origine ischémique aigüe lors de l'imagerie dJentrée (la majorité sont des CT-scan, OR=2.65 / 95% CI 1.79 - 3.92), plus d'occlusions dans l'imagerie vasculaire d'admission (OR=27.01 / 95% CI 11.5 - 62.9), moins d'anciens infarctus cérébraux sur l'imagerie (OR=0.43 / 95% 0.26¬0.72), un taux d'haemoglobine plus bas en g/1 (OR=0.97 / 95% CI 0.96 - 0.99), un taux de leucocytes plus élevé par 1000 cells/1 (OR=1.05 / 95%CI 1.00 - 1.11). parmi les 68 (28%) patients avec un devenir favorable malgré un AVC initialement sévère, leur évolution favorable à été associée avec un âge plus jeune (OR=0.94 / 95% CI 0.92 - 0.97), la présence d'évenements cérébrovasculaires antécédants (OR=3.00 / 95% CI 1.01 - 8.97), un traitement hypolipémiant déjà présent (OR= 3.82 / 95% CI 1.34 - 10.90), une température corporelle d'admission plus basse (0R=0.43 1 95% CI 0.23 - 0.78), une concentration subaigüe de glucose plus basse (OR=0.74 1 95% CI 0.56 - 0.97), et une recanalisation spontanée ou par thrombolyse à 24h (OR= 4.51 1 95%CI 1.96- 10.41). Conclusion: les AVC à présentation initiale severe sont associés à des facteurs prédicteurs cliniques, radiologiques, et métaboliques multiples, dont certains sont modifiables. Les facteurs prédicteurs des 28% de patients avec un devenir favorable en dépit d'un AVC intitialement sévère sont un pré-traitement par hypolipémiants, une temperature corporelle plus basse à l'admission, une glycémie plus basse à 24heures et la recanalisation artérielle.

The personality profile of borderline personality disordered patients using the five-factor model of personality

The purpose of this ex post facto study is to analyze the personality profile of outpatients who met criteria for borderline personality disorder according to the Five-Factor Model of personality. All patients (N = 52) completed the International Personality Disorder Examination (IPDE) Screening Questionnaire, the Big Five Questionnaire (BFQ), the Beck Depression Inventory (BDI), and the Beck Hopelessness Scale (BHS). The results show a high comorbidity with other DSM-IV-TR Axis II disorders, in particular with those from Cluster C. The BFQ average score indicates that the outpatients who met borderline criteria score lower than controls on all five dimensions, and especially on emotional stability. Correlations were computed between the BFQ and the IPDE scales in our sample. These results suggest that specific personality profile are linked to different comorbidity patterns. More than a half of our sample has clinically significant scores on Beck's scales. Surprisingly, depression and hopelessness are neither correlated with the borderline scale, nor have an effect in the relationship between personality and personality disorders.