bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of weight loss and weight regain mechanisms after Roux-en-Y gastric bypass in rats
Authors: Guijarro Ana , Suzuki Susumu , Chen Chung , Kirchner Henriette , Middleton Frank A. , Nadtochiy Sergiy , Brookes Paul S. , Niijima Akira , Inui Akio , Meguid Michael M.
Published: July 2007

Roux-en-Y gastric bypass (RYGB) is the most effective therapy for morbid obesity, but it has a ∼20% failure rate. To test our hypothesis that outcome depends on differential modifications of several energy-related systems, we used our established RYGB model in Sprague-Dawley diet-induced obese (DIO) rats to determine mechanisms contributing to successful (RGYB-S) or failed (RYGB-F) RYGB. DIO rats were randomized to RYGB, sham-operated Obese, and sham-operated obese pair-fed linked to RYGB (PF) groups. Body weight (BW), caloric intake (CI), and fecal output (FO) were recorded daily for 90 days, food efficiency (FE) was calculated, and morphological changes were determined. d-Xylose and fat absorption were studied. Glucose-stimulated vagal efferent nerve firing rates of stomach were recorded. Gut, adipose, and thyroid hormones were measured in plasma. Mitochondrial respiratory complexes in skeletal muscle and expression of energy-related hypothalamic and fat peptides, receptors, and enzymes were quantified. A 25% failure rate occurred. RYGB-S, RYGB-F, and PF rats showed rapid BW decrease vs. Obese rats, followed by sustained BW loss in RYGB-S rats. RYGB-F and PF rats gradually increased BW. BW loss in RYGB-S rats is achieved not only by RYGB-induced decreased CI and increased FO, but also via sympathetic nervous system activation, driven by increased peptide YY, CRF, and orexin signaling, decreasing FE and energy storage, demonstrated by reduced fat mass associated with the upregulation of mitochondrial uncoupling protein-2 in fat. These events override the compensatory response to the drop in leptin levels aimed at conserving energy.
Renal responses to acute reflex activation of renal sympathetic nerve activity and renal denervation in secondary hypertension
Authors: Evans Roger G. , Burke Sandra L. , Lambert Gavin W. , Head Geoffrey A.
Published: July 2007

We tested whether the responsiveness of the kidney to basal renal sympathetic nerve activity (RSNA) or hypoxia-induced reflex increases in RSNA, is enhanced in angiotensin-dependent hypertension in rabbits. Mean arterial pressure, measured in conscious rabbits, was similarly increased (+16 ± 3 mmHg) 4 wk after clipping the left ( n = 6) or right ( n = 5) renal artery or commencing a subcutaneous ANG II infusion ( n = 9) but was not increased after sham surgery ( n = 10). Under pentobarbital sodium anesthesia, reflex increases in RSNA (51 ± 7%) and whole body norepinephrine spillover (90 ± 17%), and the reductions in glomerular filtration rate (−27 ± 5%), urine flow (−43 ± 7%), sodium excretion (−40 ± 7%), and renal cortical perfusion (−7 ± 3%) produced by hypoxia were similar in normotensive and hypertensive groups. Hypoxia-induced increases in renal norepinephrine spillover tended to be less in hypertensive (1.1 ± 0.5 ng/min) than normotensive (3.7 ± 1.2 ng/min) rabbits, but basal overflow of endogenous and exogenous dihydroxyphenolglycol was greater. Renal plasma renin activity (PRA) overflow increased less in hypertensive (22 ± 29 ng/min) than normotensive rabbits (253 ± 88 ng/min) during hypoxia. Acute renal denervation did not alter renal hemodynamics or excretory function but reduced renal PRA overflow. Renal vascular and excretory responses to reflex increases in RSNA induced by hypoxia are relatively normal in angiotensin-dependent hypertension, possibly due to the combined effects of reduced neural norepinephrine release and increased postjunctional reactivity. In contrast, neurally mediated renin release is attenuated. These findings do not support the hypothesis that enhanced neural control of renal function contributes to maintenance of hypertension associated with activation of the renin-angiotensin system.
Involvement of reflex urethral closure mechanisms in urethral resistance under momentary stress condition induced by electrical stimulation of rat abdomen
Authors: Kamo Izumi , Hashimoto Tadatoshi
Published: July 2007

A novel method for evaluating the urethral resistance during abrupt elevation of abdominal pressure was developed in spinalized female rats under urethane anesthesia. Electrical stimulation of abdominal muscles for 1 s induced increases in both the intra-abdominal and the intravesical pressure in a stimulus-dependent manner, and the bladder response was almost lost when the abdomen was opened. The lowest intravesical pressure during electrical stimulation that induced fluid leakage from the urethral orifice (leak point pressure) and the maximal intravesical pressure without urine leakage below the leak point pressure were evaluated as the indexes of urethral resistance. Lower urethral resistance was obtained in the rats whose pelvic nerves or somatic nerves containing pudendal nerves and nerves to iliococcygeus/pubococcygeus muscles were transected bilaterally. In contrast, transection of bilateral hypogastric nerves showed smaller effects. Duloxetine, a drug for stress urinary incontinence, enlarged the reflex urethral closing contractions that were induced by an increase in intravesical pressure and measured using a microtip transducer catheter in the middle urethra. This drug also increased the urethral resistance (leak point pressure), whereas it did not show any effect in the rats whose pelvic nerves were bilaterally transected, showing that the augmentation of the reflex urethral closure by the drug resulted in the elevation of the urethral resistance. From these findings, it was concluded that during momentary elevation of abdominal pressure, the reflex urethral closure mechanisms via bladder-spinal cord-urethral sphincter and pelvic floor muscles greatly contribute to the increase in the urethral resistance to prevent the urinary incontinence.
Effects of hypoxia and hypercapnia on nonnutritive swallowing in newborn lambs
Authors: Duvareille Charles , Lafrance Mylène , Samson Nathalie , St-Hilaire Marie , Pladys Patrick , Micheau Philippe , Bournival Véronique , Langlois Carole , Praud Jean-Paul
Published: July 2007

The aim of the present study was to investigate the effect of hypercapnia and hypoxia on apnea and nonnutritive swallowing (NNS) frequency, as well as on the coordination between NNS and phases of the respiratory cycle in newborn lambs, while taking into account the potential effects of states of alertness. Six lambs were chronically instrumented for recording electroencephalogram, eye movements, diaphragm and thyroarytenoid muscle (a glottal adductor) activity, nasal airflow, and electrocardiogram. Polysomnographic recordings were performed in nonsedated lambs exposed to air (control), 10% O2, and 5% CO2 in a random order at 3, 4, and 5 days of age. Although hypercapnia decreased apnea frequency in wakefulness and active sleep ( P = 0.002 vs. air and hypoxia), hypoxia had no significant effect on apnea. In addition, although hypercapnia increased NNS frequency during wakefulness and quiet sleep ( P < 0.005 vs. air and hypoxia), hypoxia tended to decrease NNS frequency. Finally, only hypercapnia altered NNS-breathing coordination by increasing NNS at the transition from inspiration to expiration (ie-type NNS; P < 0.001 vs. air and hypoxia). In conclusion, whereas hypercapnia increases overall NNS frequency by specifically increasing ie-type NNS, hypoxia has the inverse tendency. Results were identical in all three states of alertness.
Activity of Vestibular Nuclei Neurons During Vestibular and Optokinetic Stimulation in the Alert Mouse
Authors: Beraneck M. , Cullen K. E.
Published: July 2007

As a result of the availability of genetic mutant strains and development of noninvasive eye movements recording techniques, the mouse stands as a very interesting model for bridging the gap among behavioral responses, neuronal response dynamics studied in vivo, and cellular mechanisms investigated in vitro. Here we characterized the responses of individual neurons in the mouse vestibular nuclei during vestibular (horizontal whole body rotations) and full field visual stimulation. The majority of neurons (∼2/3) were sensitive to vestibular stimulation but not to eye movements. During the vestibular-ocular reflex (VOR), these neurons discharged in a manner comparable to the “vestibular only” (VO) neurons that have been previously described in primates. The remaining neurons [eye-movement-sensitive (ES) neurons] encoded both head-velocity and eye-position information during the VOR. When vestibular and visual stimulation were applied so that there was sensory conflict, the behavioral gain of the VOR was reduced. In turn, the modulation of sensitivity of VO neurons remained unaffected, whereas that of ES neurons was reduced. ES neurons were also modulated in response to full field visual stimulation that evoked the optokinetic reflex (OKR). Mouse VO neurons, however, unlike their primate counterpart, were not modulated during OKR. Taken together, our results show that the integration of visual and vestibular information in the mouse vestibular nucleus is limited to a subpopulation of neurons which likely supports gaze stabilization for both VOR and OKR.
Song Selectivity in the Pallial-Basal Ganglia Song Circuit of Zebra Finches Raised Without Tutor Song Exposure
Authors: Kojima Satoshi , Doupe Allison J.
Published: July 2007

Acoustic experience critically influences auditory cortical development as well as emergence of highly selective auditory neurons in the songbird sensorimotor circuit. In adult zebra finches, these “song-selective” neurons respond better to the bird's own song (BOS) than to songs of other conspecifics. Birds learn their songs by memorizing a tutor's song and then matching auditory feedback of their voice to the tutor song memory. Song-selective neurons in the pallial-basal ganglia circuit called the anterior forebrain pathway (AFP) reflect the development of BOS. However, during learning, they also respond strongly to tutor song and are compromised in their adult selectivity when birds are prevented from matching BOS to tutor, suggesting that selectivity depends on tutor song learning as well as sensorimotor matching of BOS feedback to the tutor song memory. We examined the contribution of sensory learning of tutor song to song selectivity by recording from AFP neurons in birds reared without exposure to adult conspecifics. We found that AFP neurons in these “isolate” birds had highly tuned responses to isolate BOS. The selectivity was as high, and in the striato-pallidal nucleus Area X, even higher than that in normal birds, due to abnormally weak responsiveness to conspecific song. These results demonstrate that sensory learning of tutor song is not necessary for BOS tuning of AFP neurons. Because isolate birds develop their song via sensorimotor learning, our data further illustrate the importance of individual sensorimotor learning for song selectivity and provide insight into possible functions of song-selective neurons.
PREGS Induces LTP in the Hippocampal Dentate Gyrus of Adult Rats Via the Tyrosine Phosphorylation International Cooperative Research CREB Signaling
Authors: Chen Ling , Miyamoto Yoshiaki , Furuya Kishio , Mori Nozomu , Sokabe Masahiro
Published: July 2007

An acute application of neurosteroid pregnenolone sulfate (PREGS) to hippocampal slices from adult rats induced a long-lasting potentiation (LLPPREGS) at the perforant path-granule cell synapse. As a partial mechanism of the LLPPREGS, we previously revealed that PREGS transiently increases the probability of presynaptic glutamate release via a sensitization of α7-nicotinic acetylcholine receptor (α7nAChR). We herein demonstrate that the LLPPREGS could be separated into two independent processes: the above-mentioned early presynaptic-origin short-term potentiation (STPPREGS) and a delayed postsynaptic N-methyl-d-aspartate receptor (NMDAr)-dependent long-term potentiation termed LTPPREGS. This study focused on the analysis of the signaling mechanism underlying the LTPPREGS. PREGS increased the tyrosine phosphorylation of NR2B, a subunit of NMDAr, and the NMDAr-mediated Ca2+ influx in the granule cells. The enhanced Ca2+ influx was largely attenuated by the NR2B subunit inhibitor ifenprodil and the Src kinase family inhibitor PP2. PREGS also triggered a persistent phosphorylation of extracellular signal-regulated kinase 2 (ERK2) followed by an ERK-dependent phosphorylation of cAMP-response element-binding protein (CREB), which was crucial for the LTPPREGS induction and was sensitive to ifenprodil. These results suggest that PREGS induces an acute increase in the NR2B tyrosine phosphorylation which enhances the Ca2+ influx through NMDAr, followed by an activation of the ERK/CREB signaling cascade that leads to LTPPREGS.
Playing with Fire
Authors: Kristen Christine
Published: July 2007

Fire as an art form is evolving in the Black Rock Desert of Nevada, where many Burning Man artists explore the creation and manipulation of fire in their installations. Sculptors, engineers, geeks and pyromaniacs experiment with open fires, pressurized gases and pyrotechnics to produce mesmerizing and beautiful works of art.
Moving Through Conflict: Understanding Personal and Cultural Differences Through Movement Style
Authors: Serlin Ilene A. , Berger Miriam Roskin , Bar-Sinai Ruth
Published: July 2007

Much of human communication is nonverbal, through body and movement expression and messages. Different cultures and societies have their own nonverbal lexicons that are a crucial part of each person's individual movement patterns. Conflicts between members of different cultures that often first unconsciously arise on the nonverbal level can contribute to serious misunderstandings of another's behavior and motivation. This workshop offered participants an opportunity to explore those cultural and personal differences in movement style that may contribute to conflicts, such as those between Israelis and Palestinians. The authors use a descriptive language for human movement (Laban movement analysis) that provides objective and systematic information on “how” we move.
Bedouin—Arab Children Use Visual Art as a Response To the Destruction of Their Homes in Unrecognized Villages
Authors: Al-Krenawi Alean , Slater Nancy
Published: July 2007

This study examines the effects on Bedouin—Arab children regarding the government policy to destroy houses in the unrecognized Bedouin—Arab villages in the Negev of Israel. In this study, the Bedouin—Arab children engaged in art and story-making activities. Their responses provide new perspectives on the effects of the destruction of their homes. The sample includes 19 participants, 11- to 14-year-old boys and girls from two unrecognized villages. They were asked to draw pictures of where they live, to write a story about their drawings, and to talk about them. Using descriptive analysis, the researchers systematically examine the drawings and stories. The findings reveal that the participants have experienced negative emotional and psychological effects because of the destruction of homes and the witnessing of the ongoing destruction in their under-resourced, unrecognized villages.
Situation Invisibility and Attribution in Distributed Collaborations
Authors: Cramton Catherine Durnell , Orvis Kara L. , Wilson Jeanne M.
Published: July 2007

This article expands theoretical and empirical understanding of interpersonal relationships under distributed conditions by highlighting the importance and consequences of situation invisibility. In a laboratory study, the authors demonstrate that distributed teammates are significantly more likely than collocated teammates to make internal dispositional attributions rather than situational attributions concerning negative partner behavior because of situation invisibility. These dispositional attributions in turn affect relational outcomes such as satisfaction and cohesion. The authors also demonstrate the impact of situational explanation as an antidote to situation invisibility.
T. E. S. Scholes: the unknown Pan Africanist
Authors: Blake Kim
Published: July 2007

In the roll call of the Pan African movement, the name of Theophilus Scholes is virtually unknown. Yet this one-time Baptist missionary, who was born in Jamaica and served briefly in the Congo and on the Gold Coast, became a trenchant and influential critic of late nineteenth-century British imperialism. His attacks on the notions of `scientific racism' were similarly authoritative and his works were read and admired by leading black intellectuals and activists of the day, including Arthur Schomburg, Pixley Seme and W. E. B. Du Bois.
Abandoned and abused: prisoners in the wake of Hurricane Katrina
Authors:   National Prison Project of the American Civil Liberties Union
Published: July 2007

During Hurricane Katrina, which struck the US Gulf Coast in August 2005, thousands of men, women and children were abandoned in Orleans Parish Prison (OPP), the New Orleans jail. As the floodwaters rose in the OPP buildings, prisoners were trapped for days in locked cells without food, some standing in sewage-tainted water up to their chests, while guards left their posts. Predominantly poor African-American pre-trial detainees, held on minor charges, such as failure to pay court fees, the prisoners were eventually evacuated to various receiving facilities around the state of Louisiana, only to face systematic racial abuse, assaults and further brutality. The experiences of the OPP prisoners lay bare the routine injustices that permeate a system of incarceration that is effectively run as a profitmaking concern.
Literacy for What? Literacy for Whom? The Politics of Literacy Education and Neocolonialism in UNESCO- and World Bank–Sponsored Literacy Programs
Authors: Wickens Corrine M. , Sandlin Jennifer A.
Published: July 2007

This article explores literacy education, especially the kinds practiced and promoted by organizations such as the World Bank and the United Nations Educational, Scientific, and Cultural Organization (UNESCO), as a form of neocolonialism. Although researchers in other educational contexts have examined how schooling and education operate as a form of neocolonialism, little research has been conducted exploring this connection within adult literacy education. Using postcolonial theory and Thomas and Postlethwaite's framework for analyzing neocolonialism in educational systems, the authors present findings from a qualitative textual analysis of UNESCO- and World Bank—sponsored publicity and policy documents in which they examined two dimensions of literacy programs sponsored by UNESCO and the World Bank: (a) the purposes of literacy and (b) the funding of programs. Despite progressive shifts in how literacy is defined and practiced from colonialist Western control to local governance, for these shifts to continue, financial structures must be reorganized.
Business Improvement Districts and Small Business Advocacy: The Case of San Diego's Citywide BID Program
Authors: Stokes Robert J.
Published: July 2007

Urban analysts have pointed to the importance of neighborhood commercial districts in enhancing amenities and providing low- to mid-skill-level employment and entrepreneurial opportunities for local residents. Business improvement districts (BIDs) offer an innovation to the problem of urban commercial decline. This work addresses one key policy question: How can cities use BIDs to assist their small business base? This work differs from previous examinations of BIDs in that it addresses localized policy and administration of a citywide BID program, not collective assessments of larger BIDs nationally or theoretical issues of accountability or governance of BIDs. The case of one citywide BID program in San Diego, California, is offered as an illustration of the prospects and issues related to the use of BIDs as a small business enhancement strategy.
VEGF-A produced by chronically inflamed tissue induces lymphangiogenesis in draining lymph nodes
Authors: Halin Cornelia , Tobler Nadja E. , Vigl Benjamin , Brown Lawrence F. , Detmar Michael
Published: July 2007

Lymphangiogenesis is involved in tumor cell metastasis and plays a major role in chronic inflammatory disorders. To investigate the role of lymphangiogenesis in inflammation, we induced and maintained delayed-type hypersensitivity (DTH) reactions in the ears of mice and then analyzed the resulting lymphangiogenesis in the inflamed tissue and draining lymph nodes (LNs) by quantitative fluorescence-activated cell sorting (FACS) and by immunofluorescence. Long-lasting inflammation induced a significant increase in the number of lymphatic endothelial cells, not only in the inflamed ears but also in the ear-draining auricular LNs. Inflammation-induced lymphangiogenesis was potently blocked by systemic administration of a vascular endothelial growth factor (VEGF)-A neutralizing antibody. Surprisingly, tissue inflammation specifically induced LN lymphangiogenesis but not LN angiogenesis. These findings were explained by analysis of both VEGF-A protein and mRNA levels, which revealed that VEGF-A was expressed at high mRNA and protein levels in inflamed ears but that expression was increased only at the protein level in activated LNs. Inflammation-induced lymphangiogenesis in LNs was independent of the presence of nodal B lymphocytes, as shown in B cell-deficient mice. Our data reveal that chronic inflammation actively induces lymphangiogenesis in LNs, which is controlled remotely, by lymphangiogenic factors produced at the site of inflammation.
Effect of presenilins in the apoptosis of thymocytes and homeostasis of CD8+ T cells
Authors: Maraver Antonio , Tadokoro Carlos E. , Badura Michelle L. , Shen Jie , Serrano Manuel , Lafaille Juan J.
Published: July 2007

Many studies have positioned Notch signaling at various critical junctions during T-cell development. There is, however, debate regarding the role of Notch in the CD4 versus CD8 lineage commitment. Because there are 4 Notch receptors and RBP-Jκ–independent Notch signaling has been reported, we decided to eliminate γ-secretase activity once its activity is required for all forms of Notch signaling. T-cell–specific elimination of γ-secretase was carried out by crossing presenilin-1 (PS1) floxed mice with CD4-Cre mice and PS2 KO mice, generating PS KO mice. Thymic CD4+CD8+ double-positive (DP) cells from these mice were strikingly resistant to apoptosis by anti-CD3 treatment in vivo and expressed more Bcl-XL than control thymocytes, and deletion of only one allele of Bcl-XL gene restored wild-type levels of sensitivity to apoptosis. In addition, these PS KO animals displayed a significant decrease in the number of CD8+ T cells in the periphery, and these cells had higher level of phosphorylated p38 than cells from control littermates. Our results show that ablation of presenilins results in deficiency of CD8 cells in the periphery and a dramatic change in the physiology of thymocytes, bringing to our attention the potential side effects of presenilin inhibitors in ongoing clinical trials.
JAM-C regulates unidirectional monocyte transendothelial migration in inflammation
Authors: Bradfield Paul F. , Scheiermann Christoph , Nourshargh Sussan , Ody Christiane , Luscinskas Francis W. , Rainger G. Ed , Nash Gerard B. , Miljkovic-Licina Marijana , Aurrand-Lions Michel , Imhof Beat A.
Published: July 2007

Monocyte recruitment from the vasculature involves sequential engagement of multiple receptors, culminating in transendothelial migration and extravasation. Junctional adhesion molecule-C (JAM-C) is localized at endothelial intercellular junctions and plays a role in monocyte transmigration. Here, we show that blockade of JAM-B/-C interaction reduced monocyte numbers in the extravascular compartment through increased reverse transmigration rather than by reduced transmigration. This was confirmed in vivo, showing that an anti–JAM-C antibody reduced the number of monocytes in inflammatory tissue and increased the number of monocytes with a reverse-transmigratory phenotype in the peripheral blood. All together, our results suggest a novel mechanism of reducing accumulation of monocytes at inflammation sites by disruption of JAM-C–mediated monocyte retention.
Upregulation of pro-inflammatory cytokines in the intercostal muscles of COPD patients
Authors: Casadevall C. , Coronell C. , Ramírez-Sarmiento A. L. , Martínez-Llorens J. , Barreiro E. , Orozco-Levi M. , Gea J.
Published: July 2007

Muscle dysfunction is a characteristic feature of chronic obstructive pulmonary disease (COPD). Recent studies suggest that cytokines may operate as local regulators of both muscle function and regeneration. The aim of the present study was to characterise the expression of different cytokines in the external intercostal muscle of COPD.

Muscle biopsies were obtained from 25 stable COPD patients and eight healthy controls. Local tumour necrosis factor (TNF)-α, interleukin (IL)-1β, -6 and -10 expressions (real-time PCR and ELISA), sarcolemmal damage (immunohistochemistry), and the transcript levels of CD18 were assessed.

Muscle TNF-α and IL-6 transcripts were significantly higher in COPD patients compared with controls, and IL-1β and sarcolemmal damage showed a strong tendency in the same direction. Similar results were observed at protein level. The CD18 panleukocyte marker was similar in COPD and controls. Respiratory muscle function was impaired in COPD patients and it correlated to both the severity of lung function impairment and TNF-α muscle expression.

Chronic obstructive pulmonary disease is associated with the upregulation of pro-inflammatory cytokines in the intercostal muscles. This phenomenon might be involved in respiratory muscle dysfunction.
A novel ensemble learning method for de novo computational identification of DNA binding sites
Authors: Chakravarty Arijit , Carlson Jonathan M , Khetani Radhika S , Gross Robert H
Published: July 2007

Background

Despite the diversity of motif representations and search algorithms, thede novocomputational identification of transcription factor binding sites remains constrained by the limited accuracy of existing algorithms and the need for user-specified input parameters that describe the motif being sought.

Results

We present a novel ensemble learning method, SCOPE, that is based on the assumption that transcription factor binding sites belong to one of three broad classes of motifs: non-degenerate, degenerate and gapped motifs. SCOPE employs a unified scoring metric to combine the results from three motif finding algorithms each aimed at the discovery of one of these classes of motifs. We found that SCOPE's performance on 78 experimentally characterized regulons from four species was a substantial and statistically significant improvement over that of its component algorithms. SCOPE outperformed a broad range of existing motif discovery algorithms on the same dataset by a statistically significant margin.

Conclusion

SCOPE demonstrates that combining multiple, focused motif discovery algorithms can provide a significant gain in performance. By building on components that efficiently search for motifs without user-defined parameters, SCOPE requires as input only a set of upstream sequences and a species designation, making it a practical choice for non-expert users. A user-friendly web interface, Java source code and executables are available athttp://genie.dartmouth.edu/scope.
Bone mineral accrual and gain in skeletal width in pre-pubertal school children is independent of the mode of school transportation – one-year data from the prospective observational pediatric osteoporosis prevention (POP) study
Authors: Alwis Gayani , Linden Christian , Dencker Magnus , Stenevi-Lundgren Susanna , Gardsell Per , Karlsson Magnus K
Published: July 2007

Background

Walking and cycling to school could be an important regular source of physical activity in growing children. The aim of this 12 months prospective observational study was thus to evaluate the effect of self-transportation to school on bone mineral accrual and gain in bone width in pre-pubertal children, both traits independently contributing to bone strength.

Methods

Ninety-seven girls and 133 boys aged 7–9 years were recruited as a part of the Malmö Pediatric Osteoporosis Prevention (POP) Study in order to evaluate the influence of self-selected school transportation for the accrual of bone mineral and bone width. Children who walked or cycled to school were compared with children who went by bus or car. Bone mineral content (BMC) was measured by dual energy X-ray absorptiometry (DXA) in the lumbar spine (L2–L4), third lumbar vertebra (L3) and hip, and bone width was calculated at L3 and femoral neck (FN). Changes during the first 12 months were compared between the groups. Subjective duration of physical activity was estimated by a questionnaire and objective level of everyday physical activity at follow-up by accelerometers worn for four consecutive days. All children remained in Tanner stage 1 throughout the study. Comparisons were made by independent student'st-tests between means, ANCOVA and Fisher's exact tests.

Results

There were no differences in baseline or annual changes in BMC or bone width when the transportation groups were compared. No differences were detected in objectively measured daily level of physical activity by accelerometer. All children reached above 60 minutes of moderate to intense daily physical activity per day, the international recommended level of daily physical activity according to the United Kingdom Expert Consensus Group.

Conclusion

The everyday physical activity in these pre-pubertal children seems to be so high that the school transportation contributes little to their total level of physical activity. As a result, the choice of school transportation seems not to influence the accrual of bone mineral or gain in bone size during a 12-month follow-up period.
Trisomy 19 ependymoma, a newly recognized genetico-histological association, including clear cell ependymoma
Authors: Rousseau Emmanuel , Palm Thomas , Scaravilli Francesco , Ruchoux Marie-Magdeleine , Figarella-Branger Dominique , Salmon Isabelle , Ellison David , Lacroix Catherine , Chapon Françoise , Mikol Jacqueline , Vikkula Miikka , Godfraind Catherine
Published: July 2007

Ependymal tumors constitute a clinicopathologically heterogeneous group of brain tumors. They vary in regard to their age at first symptom, localization, morphology and prognosis. Genetic data also suggests heterogeneity. We define a newly recognized subset of ependymal tumors, the trisomy 19 ependymoma. Histologically, they are compact lesions characterized by a rich branched capillary network amongst which tumoral cells are regularly distributed. When containing clear cells they are called clear cell ependymoma. Most trisomy 19 ependymomas are supratentorial WHO grade III tumors of the young. Genetically, they are associated with trisomy 19, and frequently with a deletion of 13q21.31-31.2, three copies of 11q13.3-13.4, and/or deletions on chromosome 9. These altered chromosomal regions are indicative of genes and pathways involved in trisomy 19 ependymoma tumorigenesis. Recognition of this genetico-histological entity allows better understanding and dissection of ependymal tumors.
Noninvasive monitoring of myocardial function after surgical and cytostatic therapy in a peritoneal metastasis rat model: assessment with tissue Doppler and non-Doppler 2D strain echocardiography
Authors: Hartmann Jens , Knebel Fabian , Eddicks Stephan , Beling Mark , Grohmann Andrea , Panda Alexander , Jacobi Christoph A , Müller Joachim M , Wernecke Klaus-Dieter , Baumann Gert , Borges Adrian C
Published: July 2007

Objective

We sought to evaluate the impact of different antineoplastic treatment methods on systolic and diastolic myocardial function, and the feasibility estimation of regional deformation parameters with non-Doppler 2D echocardiography in rats.

Background

The optimal method for quantitative assessment of global and regional ventricular function in rats and the impact of complex oncological multimodal therapy on left- and right-ventricular function in rats remains unclear.

Methods

90 rats after subperitoneal implantation of syngenetic colonic carcinoma cells underwent different onclogical treatment methods and were diveded into one control group and five treatment groups (with 15 rats in each group): group 1 = control group (without operation and without medication), group 2 = operation group without additional therapy, group 3 = combination of operation and photodynamic therapy, group 4 = operation in combination with hyperthermic intraoperative peritoneal chemotherapy with mitomycine, and group 5 = operation in combination with hyperthermic intraoperative peritoneal chemotherapy with gemcitabine, group 6 = operation in combination with taurolidin i.p. instillation. Echocardiographic examination with estimation of wall thickness, diameters, left ventricular fractional shortening, ejection fraction, early and late diastolic transmitral and myocardial velocities, radial and circumferential strain were performed 3–4 days after therapy.

Results

There was an increase of LVEDD and LVESD in all groups after the follow-up period (P = 0.0037). Other LV dimensions, FS and EF as well as diastolic mitral filling parameters measured by echocardiography were not significantly affected by the different treatments. Values for right ventricular dimensions and function remained unchanged, whereas circumferential 2D strain of the inferior wall was slightly, but significantly reduced under the treatment (-18.1 ± 2.5 before and -16.2 ± 2.9 % after treatment; P = 0.001) without differences between the single treatment groups.

Conclusion

It is feasible to assess dimensions, global function, and regional contractility with echocardiography in rats under different oncological therapy. The deformation was decreased under overall treatment without influence by one specific therapy. Therefore, deformation assessment with non-Doppler 2D strain echocardiography is more sensitive than conventional echocardiography for assessing myocardial dysfunction in rats under oncological treatment.
Corticortophin releasing factor 2 receptor agonist treatment significantly slows disease progression in mdx mice
Authors: Hinkle Richard T , Lefever Frank R , Dolan Elizabeth T , Reichart Deborah L , Dietrich Jefferey A , Gropp Kathryn E , Thacker Robert I , Demuth Jeffrey P , Stevens Paula J , Qu Xiaoyan A , Varbanov Alex R , Wang Feng , Isfort Robert J
Published: July 2007

Background

Duchenne muscular dystrophy results from mutation of the dystrophin gene, causing skeletal and cardiac muscle loss of function. The mdx mouse model of Duchenne muscular dystrophy is widely utilized to evaluate the potential of therapeutic regimens to modulate the loss of skeletal muscle function associated with dystrophin mutation. Importantly, progressive loss of diaphragm function is the most consistent striated muscle effect observed in the mdx mouse model, which is the same as in patients suffering from Duchenne muscular dystrophy.

Methods

Using the mdx mouse model, we have evaluated the effect that corticotrophin releasing factor 2 receptor (CRF2R) agonist treatment has on diaphragm function, morphology and gene expression.

Results

We have observed that treatment with the potent CRF2R-selective agonist PG-873637 prevents the progressive loss of diaphragm specific force observed during aging of mdx mice. In addition, the combination of PG-873637 with glucocorticoids not only prevents the loss of diaphragm specific force over time, but also results in recovery of specific force. Pathological analysis of CRF2R agonist-treated diaphragm muscle demonstrates that treatment reduces fibrosis, immune cell infiltration, and muscle architectural disruption. Gene expression analysis of CRF2R-treated diaphragm muscle showed multiple gene expression changes including globally decreased immune cell-related gene expression, decreased extracellular matrix gene expression, increased metabolism-related gene expression, and, surprisingly, modulation of circadian rhythm gene expression.

Conclusion

Together, these data demonstrate that CRF2R activation can prevent the progressive degeneration of diaphragm muscle associated with dystrophin gene mutation.
Effectsof Aspergillus fumigatusgliotoxin and methylprednisolone on human neutrophils: implications for the pathogenesis of invasive aspergillosis
Authors: Orciuolo Enrico , Stanzani Marta , Canestraro Martina , Galimberti Sara , Carulli Giovanni , Lewis Russell , Petrini Mario , Komanduri Krishna V
Published: July 2007

Aspergillus fumigatus (AF) is a ubiquitous mold and the most common cause of invasive aspergillosis (IA) in immunocompromised patients. In stem cell transplant recipients, IA now occurs most frequently in the setting of therapy with corticosteroids, including methylprednisolone (MP). We showed previously that gliotoxin (GT), an AF-derived mycotoxin, induces apoptosis in monocytes and dendritic cells, resulting in the suppression of AF-specific T cell responses. We examined the ability of GT to induce apoptosis in polymorphonuclear leukocytes (PMN) and assessed GT effects on important neutrophil functions, including phagocytic function, degranulation, myeloperoxidase activity, and the production of reactive oxygen species (ROS). In contrast to its effects on monocytes, PMN remained resistant to GT-mediated apoptosis. Although many essential neutrophil functions were unaffected, GT inhibited phagocytosis and also induced a decrease in ROS generation by PMN. In contrast, MP therapy potentiated ROS production, suggesting a mechanism that may facilitate tissue injury in IA. Distinct from its effects on untreated PMN, GT augmented ROS production in MP-treated PMN. Our results suggest that although GT may suppress the adaptive immune response, GT may also serve to increase PMN-mediated inflammation, which is likely to play an important role in tissue destruction in the setting of IA.
Chorionic gonadotropin can enhance innate immunity by stimulating macrophage function
Authors: Wan Hui , Versnel Marjan A , Cheung Wai yee , Leenen Pieter J M , Khan Nisar A , Benner Robbert , Kiekens Rebecca C M
Published: July 2007

Human chorionic gonadotropin (hCG) is a placental glycoprotein, mainly secreted by trophoblasts during pregnancy. Its function in endocrine regulation has been well documented, but its immunological role is still largely unclear. For a successful pregnancy, an effective innate immunity is needed to protect the mother and fetus against infection, while maintaining tolerance against the paternal antigens of the fetus. The aim of this study was to investigate the effect of hCG on the function of macrophages (Mϕ), which are major players in the innate response. hCG treatment of IFN-γ-primed Mϕ resulted in increased production of NO, reactive oxygen species, IL-6 and IL-12p40, and enhanced phagocytosis of apoptotic cells. hCG treatment did not affect the induction of allogeneic T cell proliferation by IFN-γ-primed Mϕ. The observed effects were receptor-mediated and involved the protein kinase A signaling pathway, as indicated by blocking studies using specific inhibitors. In vivo thioglycollate-elicited Mϕ also exhibited increased phagocytic ability upon IFN-γ activation and hCG treatment. In conclusion, hCG enhances Mϕ functions involved in innate immunity, while the capacity to stimulate allogeneic T cells remains unchanged.
Tolerization with BLP down-regulates HMGB1—a critical mediator of sepsis-related lethality
Authors: Coffey J Calvin , Wang Jiang Huai , Kelly Ray , Romics Laszlo , O’Callaghan Adrian , Fiuza Carmen , Redmond H Paul
Published: July 2007

Tolerization with bacterial lipoprotein (BLP) affords a significant survival benefit in sepsis. Given that high mobility group box protein-1 (HMGB1) is a recognized mediator of sepsis-related lethality, we determined if tolerization with BLP leads to alterations in HMGB1. In vitro, BLP tolerization led to a reduction in HMGB1 gene transcription. This was mirrored at the protein level, as HMGB1 protein expression and release were reduced significantly in BLP-tolerized human THP-1 monocytic cells. BLP tolerance in vivo led to a highly significant, long-term survival benefit following challenge with lethal dose BLP in C57BL/6 mice. This was associated with an attenuation of HMGB1 release into the circulation, as evidenced by negligible serum HMGB1 levels in BLP-tolerized mice. Moreover, HMGB1 levels in peritoneal macrophages from BLP-tolerized mice were reduced significantly. Hence, tolerization with BLP leads to a down-regulation of HMGB1 protein synthesis and release. The improved survival associated with BLP tolerance could thus be explained by a reduction in HMGB1, were the latter associated with lethality in BLP-related sepsis. In testing this hypothesis, it was noted that neutralization of HMGB1, using anti-HMGB1 antibodies, abrogated BLP-associated lethality almost completely. To conclude, tolerization with BLP leads to a down-regulation of HMGB1, thus offering a novel means of targeting the latter. HMGB1 is also a mediator of lethality in BLP-related sepsis.
Evaluation and suggested improvements of the Biopharmaceutics Classification System (BCS)
Authors: Fagerholm Urban
Published: July 2007

This review has evaluated the Biopharmaceutics Classification System (BCS) and improvements have been proposed. The BCS has a very strict solubility/dissolution limit, a generous Pe-limit (≥ 14-times higher rate constant limit for dissolution than for permeation), and is stricter for drugs with a long half-life (t1/2). Available human in-vivo, in-vitro, and in-silico Pe-methods cannot classify Pe for moderately to highly permeable substances sufficiently well, and in-vitro data often underpredict the in-vivo dissolution potential and rate. Good in-vivo dissolution and absorption can be expected for most high Pe drug products. It has not been possible to find a highly permeable product with a Dose number (Do) < 385 (< 2400 in the fed state) that is clearly incompletely absorbed, and near complete uptake has been shown for a drug product with a Do of 660000. The potential implication of these findings is that many true BCS Class I drug products are incorrectly classified. This could be a reason for the limited use of this system. On this basis, it has been suggested that: the limit for high for solubility/dissolution is decreased (to >40 and >95% dissolved within 30min and 3 h, respectively); the limit for high Pe is increased (to >Pe of metoprolol); accurate Pe-models or in-vivo fraction absorbed data are used; solubility/dissolution tests are performed using real or validated simulated gastrointestinal fluids; in-vitro/in-vivo dissolution relationships are established; the t½ is considered; and the rate-limiting step for in-vivo absorption is determined. A major change could be to reduce the BCS into two classes: permeation-rate (Class I) or dissolution-rate (Class II) limited absorption. It is believed that this could give a better balance and increase the number of biowaivers.
Microemulsions as topical delivery vehicles for the anti-melanoma prodrug, temozolomide hexyl ester (TMZA-HE)
Authors: Suppasansatorn Panassaya , Nimmannit Ubonthip , Conway Barbara R , Du Lingran , Wang Yongfeng
Published: July 2007

A prodrug, temozolomide acid hexyl ester (TMZA-HE), was identified as a skin-deliverable congener for temozolomide (TMZ) to treat skin cancers. Poor solubility and instability of TMZA-HE rendered a serious challenge for formulation of a topical preparation. Microemulsions (ME) were chosen as a potential vehicle for TMZA-HE topical preparations. ME systems were constructed with either oleic acid (OA) or isopropyl myristate (IPM) as the oil phase and tocopheryl (vitamin E) polyethylene glycol 1000 succinate (VE-TPGS) as a surfactant. Topical formulations of OA and IPM ME systems demonstrated beneficial solubilising ability and provided a stable environment for the prodrug, TMZA-HE. Significant differences between the microstructures of OA and IPM ME systems were revealed by freeze fracture electron microscopy (FFEM) and different loading abilities and permeation potencies between the two systems were also identified. In permeation studies, IPM ME systems, with inclusion of isopropyl alcohol (IPA) as a co-surfactant, significantly increased TMZA-HE permeation through silicon membranes and rat skin resulting in less drug retention within the skin, while OA ME systems demonstrated higher solubilising ability and a higher concentration of TMZA-HE retained within the skin. Therefore IPM ME systems are promising for transdermal delivery of TMZA-HE and OA ME systems may be a suitable choice for a topical formulation of TMZA-HE.
Heterologous up-regulation of the histamine H1 receptor by M3 muscarinic receptor-mediated activation of H1-receptor gene transcription
Authors: Miyoshi Katsuhiro , Kawakami Nozomi , Das Asish Kumar , Fujimoto Katsumi , Horio Shuhei , Fukui Hiroyuki
Published: July 2007

Histamine H1 receptor (H1R) level varies under various pathological conditions, and these changes may be responsible for some pathogenesis, such as allergic rhinitis. Previously, we showed that H1R was heterologously down-regulated (through degradation of H1R) by prolonged stimulation with muscarinic M3 receptor (M3R) in Chinese hamster ovary (CHO) cells stably expressing H1R and M3R. However, this cell was inadequate for studying the effects on H1R gene regulation, because the cell expresses H1R, which is under the control of the SV40 promoter. Therefore, in this study, we have investigated the possible role of M3R stimulation in the H1R gene transcription and H1R mRNA stability by using U373 astrocytoma cells that express endogenous H1R and transfected M3R. Stimulation of M3R significantly increased H1R promoter activity and H1R mRNA level without alteration in H1R mRNA stability. The H1R level was also up-regulated by M3R activation (150% of control by treatment with carbachol for 24 h). These M3R-mediated events were almost completely blocked by the protein kinase C (PKC) inhibitor, Ro 31–8220, suggesting the involvement of PKC. These results indicated that M3R was involved in the up-regulation of H1R by activating H1R gene transcription through a PKC-dependent process.
Characterizing residual stresses in rectangular beam specimens following thermomechanical loading
Authors: Mirzaee-Sisan A , Smith D. J , Truman C. E
Published: July 2007

Edge welding and partial quenching are explored as two processes capable of generating well-defined residual stress fields in beam specimens. The purpose of introducing residual stress fields into test specimens is to allow the influence of pre-existing residual stresses on the fracture behaviour of metallic components under applied loads to be studied in a systematic manner. Three materials are considered in this paper: two stainless steels (type 316H and Esshete 1250) and one ferritic steel (A533B). The paper presents both numerical and experimental results. The numerical results were obtained using finite element analysis, and the experimental measurements made primarily with the neutron diffraction technique, and also with X-ray synchrotron diffraction and incremental centre hole drilling. There was, in many cases, good agreement between predictions and measurements; however, there were several instances where finite element predictions differed significantly from measurements. This difference was often most pronounced close to the edge-welded or partially quenched specimen edge where the sensitivity of the numerical models to the assumed thermal and mechanical boundary conditions was greatest. The results presented confirm the usefulness of these two processes as a means of introducing residual stress fields into test specimens but highlight the need for experimental validation of numerical models. It is also demonstrated that, if a crack is subsequently introduced into the specimens, it is possible to generate both tensile and compressive crack-tip residual stress states.