bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enzastaurin‐induced apoptosis in glioma cells is caspase‐dependent and inhibited by BCL‐XL
Authors: Rieger Johannes , Lemke Dieter , Maurer Gabriele , Weiler Markus , Frank Brigitte , Tabatabai Ghazaleh , Weller Michael , Wick Wolfgang 
Published: July 2008

AbstractThe novel protein kinase C‐β inhibitor enzastaurin (ENZA) induced apoptosis in LNT‐229 and T98G cells whereas A172 cells were resistant. Further, ENZA reduced proliferation in glioblastoma‐initiating cells T 269 and T 323 but did not induce apoptosis. ENZA‐induced apoptosis involved cleavage of caspases 3, 8, and 9 and led to mitochondrial cytochrome c release and was strongly suppressed by the broad spectrum caspase inhibitor zVAD‐fmk but only slightly by the expression of the viral caspase 1/8 inhibitor cytokine response modifier‐A. ENZA did not reduce the phosphorylation of protein kinase B (Akt), but of p70 S6 kinase and of its substrate S6 protein in T98G cells. Inhibition of the phosphatidylinositol 3 kinase signaling pathway did not restore sensitivity of A172 cells towards ENZA, and constitutively active Akt did not protect LNT‐229 and T98G cells from ENZA‐induced apoptosis. Dephosphorylation of glycogen synthase kinase 3β, a biomarker of ENZA action, and cell death induction by ENZA were separately regulated. Inhibition or activation of Akt only weakly modulated ENZA‐induced dephosphorylation of glycogen synthase kinase 3β. In ENZA‐resistant A172 cells, apoptosis ligand 2 (Apo2L.0)‐induced cleavage of caspases 3, 8, and 9 was increased by ENZA, resulting in synergistic activity of ENZA and Apo2L.0.
Altered pharmacology in the intensive care unit patient
Authors: Zagli Giovanni , Tarantini Francesca , Bonizzoli Manuela , Di Filippo Alessandro , Peris Adriano , De Gaudio Angelo Raffaele , Geppetti Pierangelo 
Published: July 2008

AbstractCritically ill patients, not infrequently present alterations of physiological parameters that determine the success/failure of therapeutic interventions as well as the final outcome. Sepsis and polytrauma are two of the most common and complex syndromes occurring in Intensive Care Unit (ICU) and affect drug absorption, disposition, metabolism and elimination. Pharmacological management of ICU patients requires consideration of the unique pharmacokinetics associated with these clinical conditions and the likely occurrence of drug interaction. Rational adjustment in drug choice and dosing contributes to the appropriateness of treatment of those patients.
Dysfunction of astrocytes in senescence‐accelerated mice SAMP8 reduces their neuroprotective capacity
Authors: García‐Matas Silvia , Gutierrez‐Cuesta Javier , Coto‐Montes Ana , Rubio‐Acero Raquel , Díez‐Vives Cristina , Camins Antoni , Pallàs Mercè , Sanfeliu Coral , Cristòfol Rosa 
Published: July 2008

SummaryEarly onset increases in oxidative stress and tau pathology are present in the brain of senescence‐accelerated mice prone (SAMP8). Astrocytes play an essential role, both in determining the brain's susceptibility to oxidative damage and in protecting neurons. In this study, we examine changes in tau phosphorylation, oxidative stress and glutamate uptake in primary cultures of cortical astrocytes from neonatal SAMP8 mice and senescence‐accelerated‐resistant mice (SAMR1). We demonstrated an enhancement of abnormally phosphorylated tau in Ser199 and Ser396 in SAMP8 astrocytes compared with that of SAMR1 control mice. Gsk3β and Cdk5 kinase activity, which regulate tau phosphorylation, was also increased in SAMP8 astrocytes. Inhibition of Gsk3β by lithium or Cdk5 by roscovitine reduced tau phosphorylation at Ser396. Moreover, we detected an increase in radical superoxide generation, which may be responsible for the corresponding increase in lipoperoxidation and protein oxidation. We also observed a reduced mitochondrial membrane potential in SAMP8 mouse astrocytes. Glutamate uptake in astrocytes is a critical neuroprotective mechanism. SAMP8 astrocytes showed a decreased glutamate uptake compared with those of SAMR1 controls. Interestingly, survival of SAMP8 or SAMR1 neurons cocultured with SAMP8 astrocytes was significantly reduced. Our results indicate that alterations in astrocyte cultures from SAMP8 mice are similar to those detected in whole brains of SAMP8 mice at 1–5 months. Moreover, our findings suggest that this in vitro preparation is suitable for studying the molecular and cellular processes underlying early aging in this murine model. In addition, our study supports the contention that astrocytes play a key role in neurodegeneration during the aging process.
Repression of the SUMO‐specific protease Senp1 induces p53‐dependent premature senescence in normal human fibroblasts
Authors: Yates Kristin E. , Korbel Gregory A. , Shtutman Michael , Roninson Igor B. , DiMaio Daniel 
Published: July 2008

SummaryThe proliferative lifespan of normal somatic human cells in culture terminates in a permanent growth‐arrested state known as replicative senescence. In this study, we show that RNA interference‐mediated repression of the genes encoding the small ubiquitin‐related modifier (SUMO)‐specific proteases, Senp1, Senp2, and Senp7, induced low passage primary human fibroblasts to senesce rapidly. Following Senp1 repression, we observed a global increase in sumoylated proteins and in the number and size of nuclear SUMO‐containing promyelocytic leukemia (PML) bodies. SUMO/PML bodies also increased during replicative senescence. p53 transcriptional activity was enhanced towards known p53 target genes following repression of Senp1, and inhibition of p53 function prevented senescence after Senp1 repression. These data indicate that Senp1 repression induces p53‐mediated premature senescence and that SUMO proteases may thus be required for proliferation of normal human cells.
Different rates of telomere attrition in peripheral lymphocytes in a pair of dizygotic twins with hematopoietic chimerism
Authors: Brüderlein Silke , Müller Kathrin , Melzner Julia , Högel Josef , Wiegand Peter , Möller Peter 
Published: July 2008

SummaryHematopoietic chimerism in dizygotic twins is due to placental vascular anastomoses and arises when hematopoietic stem cells from one twin home to the bone marrow of the other. We report a case of hematopoietic chimerism in a pair of 27‐year‐old dizygotic twins who each had a mixture of 46,XX and 46,XY blood lymphocytes, both with 98% male (XY) lymphocytes and 2% female (XX) lymphocytes. Analysis of telomere length by T/C FISH revealed that the female twin generally had longer telomeres than the male twin. Moreover, in the male sibling, the telomeres within the female lymphocytes were shortened to 87% of their original length, while the telomeres within the male lymphocytes were 33% longer in the female sibling. Thus, telomere length attrition in peripheral lymphocytes is determined mainly by the environment of the cell and less by intracellular factors.
Resting Brain Glucose Uptake in Headache‐Free Migraineurs
Authors: Kassab Mounzer , Bakhtar Omid , Wack David , Bednarczyk Edward 
Published: July 2008

Background and Objective.— To compare metabolism in the brains of migraineurs during headache‐free periods with those obtained from healthy volunteers.Methods.— Eleven migraineurs (defined by the International Headache Society's criteria) presented during spontaneous headache‐free intervals to undergo 18FDG PET brain imaging of glucose metabolism. The control group consisted of 14 healthy volunteers. Comparison of images was done using Statistical Parametric Mapping to detect significant (P < .05) differences in brain glucose metabolism between the 2 groups.Results.— Two regions of significant increase in glucose uptake were identified in migraineurs relative to the control population. The 2 regions were mapped predominantly to the posterior white matter of the cerebrum and cerebellum.Conclusions.— Our study demonstrates the presence of what may be a primary metabolic disturbance in the posterior white matter of the brain in migraineurs.
Effect of stage 2 kindling on local cerebral blood flow rates in rats with genetic absence epilepsy
Authors: Çarçak Nihan , Ferrandon Arielle , Koning Estelle , Aker Rezzan Gülhan , Özdemir Osman , Onat Filiz Yilmaz , Nehlig Astrid 
Published: July 2008

SummaryPurpose:  Genetic absence epilepsy rats from Strasbourg (GAERS) are resistant to the progression of kindling seizures. We studied local cerebral blood flow (LCBF) changes in brain regions involved in seizures in both GAERS and nonepileptic rats (NEC) to map the differences that may be related to the resistance to kindling.Methods:  Electrodes were implanted in the amygdala of adult NEC and GAERS male rats, which were stimulated to reach stage 2. Quantitative autoradiographic measurements of LCBF were performed by the [14C]‐iodoantipyrine ([14C]IAP) autoradiographic technique allowing the precise mapping of regional perfusion changes. LCBF rates were measured bilaterally in 43 brain regions. The tracer infusion lasted for 60 s and started at 15 s before seizure induction.Results:  Rates of LCBF increased in stimulated GAERS and NEC groups compared to nonstimulated controls. The LCBF increase in stimulated GAERS was larger and more widespread than that observed in stimulated NEC. The LCBF increase in the somatosensory cortex, ventrobasal and anterior thalamic nuclei, hypothalamus, subthalamic nucleus, piriform, entorhinal and perirhinal cortex, amygdala, CA2 region of hippocampus, and substantia nigra was statistically significantly larger in stimulated GAERS compared to stimulated NEC rats.Conclusion:  The results show that more brain regions are activated by kindling stimulation in GAERS. This widespread activation in GAERS involves the somatosensory cortex and thalamus, which are both known to be involved in the expression of absence seizures as well as numerous limbic regions thought not to play a role in the expression of absence seizures, suggesting an interaction between corticothalamocortical and limbic circuitries.
EEG‐fMRI study of the ictal and interictal epileptic activity in patients with eyelid myoclonia with absences
Authors: Liu Yonghong , Yang Tianhua , Liao Wei , Yang Xuhong , Liu Iing , Yan Bo , Chen Huafu , Gong Qiyong , Stefan Hermann , Zhou Dong 
Published: July 2008

SummaryPurpose:  To investigate the blood oxygenation level‐dependent (BOLD) signal changes correlated with ictal and interictal epileptic discharges using electroencephalography‐correlated functional magnetic resonance imaging (EEG‐fMRI) in patients with eyelid myoclonia with absences (EMA) and then to explore the pathophysiological mechanisms of epileptic discharges and their effect on brain function.Methods:  Four patients with EMA were investigated through the method of EEG‐fMRI. The characteristics of BOLD signal changes linked to ictal and interictal epileptic discharges under different states of consciousness were explored.Results:  Seven sessions of EEG‐fMRI scanning in the four patients were obtained. The main regions of activation included thalamus, mesial frontal cortex, middle parietal lobe, temporal lobe, insula, midline structures, and cerebellum. Deactivations were mainly in the anterior frontal lobe, posterior parietal lobe, and posterior cingulate gyrus. Thalamic BOLD change was predominantly activation in most of our cases. The distribution of activation associated with ictal epileptic discharges was wider, and the distribution of deactivation was closer to pericortex compared with the BOLD change linked with interictal epileptic discharges.Conclusions:  The activation in the thalamus may be associated with generalized spike wave in EMA; the combination of different patterns of activation with consistent pattern of deactivations (“default” pattern) in patients with EMA may prognosticate different states of consciousness in response to ictal and interictal epileptic discharges.
EVALUATION OF ANTIOXIDANT DEFENSE RESPONSES TO LEAD STRESS IN HAPALOSIPHON FONTINALIS‐3391
Authors: Zutshi Sunaina , Choudhary Meenakshi , Bharat Naveen , Abdin Malik Zainul , Fatma Tasneem 
Published: July 2008

Lead (Pb) is a heavy metal and a potentially hazardous environmental pollutant. In this study, the potential of lead to induce oxidative stress in biological systems was assessed using the cyanobacterium Hapalosiphon fontinalis‐339 as model test organism. The impact of lead toxicity on the cellular antioxidant system and the biochemical modulations that result in generation of antioxidant defense responses were also studied. To determine the effect of Pb toxicity, the test organism was grown in the presence of various concentrations (0.05, 0.10, 0.20, 0.40, 0.80, 1.0, 1.20, and 1.25 mg · L−1) of exogenous lead chloride (PbCl2), and its effects on growth were observed in terms of the change in chl content. There was a significant increase in metal uptake by the alga with a concomitant decrease in growth. Lead stress appeared to significantly up‐regulate the levels of stress‐related antioxidant enzymes—such as superoxide dismutase (SOD), ascorbate peroxidase (APX), and glutathione reductase (GR)—while a decrease in catalase (CAT) levels was observed. In addition, the levels of nonenzymatic antioxidants, oxidized and total glutathione, were changed. Our results suggest the existence of a potent antioxidant defense machinery in H. fontinalis‐339 and this organism can be employed to monitor lead toxicity in the environment.
INFLUENCE OF IRRADIANCE ON VIRUS–ALGAL HOST INTERACTIONS1
Authors: Baudoux Anne‐Claire , Brussaard Corina P. D. 
Published: July 2008

The effect of different irradiance levels on the interactions between the algal host and its virus was investigated for two marine phytoplankton, Phaeocystis globosa Scherff. and Micromonas pusilla (Butcher) Manton et Parke. The algal cultures were acclimated at 25, 100, and 250 μmol photons · m−2 · s−1 (LL, ML, and HL, respectively), after which they were infected with a lytic virus (PgV‐07T and MpV‐02T) and monitored under the appropriate irradiance and in darkness. The effect of irradiance levels on the host–virus interactions differed for the two algal host–virus systems examined. For P. globosa, the LL‐acclimated cultures showed a 4 h prolonged latent period (11–16 h), which may be related to the subsaturated growth observed at this irradiance. The burst size was reduced by 50% at LL and HL compared to ML (525 PgV · cell−1). The fraction of infectious viruses, however, remained unchanged. Viral replication was prevented when the LL P. globosa cultures were kept in darkness (up to 48 h) but recovered when placed back into the light. PgV‐07T still replicated in the dark for the ML‐ and HL‐acclimated cultures, but viral yield was reduced by 50%–85%. For M. pusilla, the burst size (285–360 MpV · cell−1), the infectivity, and the latent period of MpV‐02T (7–11 h) remained unaffected by the incident light. Conversely, darkness not only inhibited MpV replication but also resulted in substantial cell lysis of the noninfected cultures. Our study implies that irradiance level is an important factor controlling algal host–virus interactions and hence the dynamics of phytoplankton populations.
Environmental Enrichment Alters Neurotrophin Levels After Fetal Alcohol Exposure in Rats
Authors: Parks Elizabeth A. , McMechan Andrew P. , Hannigan John H. , Berman Robert F. 
Published: July 2008

Background:  Prenatal alcohol exposure causes abnormal brain development, leading to behavioral deficits, some of which can be ameliorated by environmental enrichment. As both environmental enrichment and prenatal alcohol exposure can individually alter neurotrophin expression, we studied the interaction of prenatal alcohol and postweaning environmental enrichment on brain neurotrophin levels in rats.Methods:  Pregnant rats received alcohol by gavage, 0, 4, or 6 g/kg/d (Zero, Low, or High groups), or no treatment (Naïve group), on gestational days 8 to 20. After weaning on postnatal day 21, offspring were housed for 6 weeks in Isolated, Social, or Enriched conditions. Levels of nerve growth factor (NGF), brain‐derived neurotrophic factor (BDNF), and neurotrophin‐3 (NT‐3) were then measured in frontal cortex, occipital cortex, hippocampus, and cerebellar vermis.Results:  Prenatal alcohol exposure increased NGF levels in frontal cortex (High‐dose group) and cerebellar vermis (High‐ and Low‐dose groups); increased BDNF in frontal cortex, occipital cortex and hippocampus (Low‐dose groups), and increased NT‐3 in hippocampus and cerebellar vermis (High‐dose). Environmental enrichment resulted in lower NGF, BDNF, and NT‐3 levels in occipital cortex and lower NGF in frontal cortex. The only significant interaction between prenatal alcohol treatment and environment was in cerebellar vermis where NT‐3 levels were higher for enriched animals after prenatal alcohol exposure, but not for animals housed under Isolated or Social conditions.Conclusions:  Both prenatal alcohol exposure and postweaning housing conditions alter brain neurotrophin levels, but the effects appear to be largely independent. Although environmental enrichment can improve functional outcomes, these results do not provide strong support for the hypothesis that rearing in a complex environment ameliorates prenatal alcohol effects on brain neurotrophin levels in rats.
Role of Acetaldehyde in Ethanol‐Induced Elevation of the Neuroactive Steroid 3α‐Hydroxy‐5α‐Pregnan‐20‐One in Rats
Authors: Boyd Kevin N. , O’Buckley Todd K. , Leslie Morrow A. 
Published: July 2008

Background:  Systemic ethanol administration increases neuroactive steroid levels that increase ethanol sensitivity. Acetaldehyde is a biologically active compound that may contribute to behavioral and rewarding effects of ethanol. We investigated the role of acetaldehyde in ethanol‐induced elevations of 3α‐hydroxy‐5α‐pregnan‐20‐one (3α,5α‐THP) levels in cerebral cortex.Methods:  Male Sprague–Dawley rats were administered ethanol, and plasma acetaldehyde concentrations were measured by gas chromatography to determine relevant concentrations. Rats were then administered acetaldehyde directly, acetaldehyde plus cyanamide to block its degradation, or ethanol in the presence of inhibitors of ethanol metabolism, to determine effects on 3α,5α‐THP levels in cerebral cortex.Results:  Ethanol administration (2 g/kg) to rats results in a peak acetaldehyde concentration of 6‐7 μM at 10 minutes that remains stable for the duration of the time points tested. Direct administration of acetaldehyde eliciting this plasma concentration does not increase cerebral cortical 3α,5α‐THP levels, and inhibition of ethanol‐metabolizing enzymes to modify acetaldehyde formation does not alter ethanol‐induced 3α,5α‐THP levels. However, higher doses of acetaldehyde (75 and 100 mg/kg), in the presence of cyanamide to prevent its metabolism, are capable of increasing cortical 3α,5α‐THP levels.Conclusions:  Physiological concentrations of acetaldehyde are not responsible for ethanol‐induced increases in 3α,5α‐THP, but a synergistic role for acetaldehyde with ethanol may contribute to increases in 3α,5α‐THP levels and ethanol sensitivity.
Age‐ and Sex‐Dependent Effects of Footshock Stress on Subsequent Alcohol Drinking and Acoustic Startle Behavior in Mice Selectively Bred for High‐Alcohol Preference
Authors: Chester Julia A. , Barrenha Gustavo D. , Hughes Matthew L. , Keuneke Kelly J. 
Published: July 2008

Background: Exposure to stress during adolescence is known to be a risk factor for alcohol‐use and anxiety disorders. This study examined the effects of footshock stress during adolescence on subsequent alcohol drinking in male and female mice selectively bred for high‐alcohol preference (HAP1 lines). Acoustic startle responses and prepulse inhibition (PPI) were also assessed in the absence of, and immediately following, subsequent footshock stress exposures to determine whether a prior history of footshock stress during adolescence would produce enduring effects on anxiety‐related behavior and sensorimotor gating.Methods: Alcohol‐naïve, adolescent (male,n = 27; female,n = 23) and adult (male,n = 30; female,n = 30) HAP1 mice were randomly assigned to a stress or no stress group. The study consisted of 5 phases: (1) 10 consecutive days of exposure to a 30‐minute footshock session, (2) 1 startle test, (3) one 30‐minute footshock session immediately followed by 1 startle test, (4) 30 days of free‐choice alcohol consumption, and (5) one 30‐minute footshock session immediately followed by 1 startle test.Results: Footshock stress exposure during adolescence, but not adulthood, robustly increased alcohol drinking behavior in both male and female HAP1 mice. Before alcohol drinking, females in both the adolescent and adult stress groups showed greater startle in phases 2 and 3; whereas males in the adolescent stress group showed greater startle only in phase 3. After alcohol drinking, in phase 5, enhanced startle was no longer apparent in any stress group. Males in the adult stress group showed reduced startle in phases 2 and 5. PPI was generally unchanged, except that males in the adolescent stress group showed increased PPI in phase 3 and females in the adolescent stress group showed decreased PPI in phase 5.Conclusions: Adolescent HAP1 mice appear to be more vulnerable to the effects of footshock stress than adult mice, as manifested by increased alcohol drinking and anxiety‐related behavior in adulthood. These results in mice suggest that stress exposure during adolescence may increase the risk for developing an alcohol‐use and/or anxiety disorder in individuals with a genetic predisposition toward high alcohol consumption.
The Effects of Patient Function and Dependence on Costs of Care in Alzheimer's Disease
Authors: Zhu Carolyn W. , Leibman Christopher , McLaughlin Trent , Scarmeas Nikolaos , Albert Marilyn , Brandt Jason , Blacker Deborah , Sano Mary , Stern Yaakov 
Published: July 2008

OBJECTIVES: To estimate incremental effects of patients' dependence and function on costs of care during the early stages of Alzheimer's disease (AD) and to compare strengths of their relationships with different cost components.DESIGN: Multicenter, cross‐sectional, observational study.SETTING: Three university hospitals in the United States.PARTICIPANTS: One hundred seventy‐nine community‐living patients with probable AD, with modified Mini‐Mental State Examination scores of 30 or higher.MEASUREMENTS: Patients' dependence was measured using the Dependence Scale (DS). Functional capacity was measured using the Blessed Dementia Rating Scale (BDRS). Total cost was measured by summing direct medical costs and informal costs. Direct medical costs included costs of hospitalization, outpatient treatment and procedures, assistive devices, and medications. Informal costs were estimated from time spent helping with basic and instrumental activities of daily living for up to three caregivers per patient using national average hourly earnings as wage rate.RESULTS: DS and BDRS were associated with higher total cost; a 1‐point increase in DS was associated with a $1,832 increase in total cost, and a 1‐point increase in BDRS was associated with a $3,333 increase. Examining component costs separately identified potential differences between DS and BDRS. A 1‐point increase in BDRS was associated with a $1,406 increase in direct medical cost. A 1‐point increase in DS was associated with a $1,690 increase in informal cost.CONCLUSION: Patients' dependence and function related differently to direct medical and informal cost, suggesting that measures of function and dependence provided unique information for explaining variations in cost of care for patients with AD, highlighting the value in measuring both constructs.