bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multicenter study of sleep‐wake rhythm disorders: Therapeutic effects of vitamin B12, bright light therapy, chronotherapy and hypnotics
Authors: YAMADERA HIROSHI , TAKAHASHI KIYOHISA , OKAWA MASAKO 
Published: March 2008

AbstractOne hundred and six subjects with primary sleep‐wake rhythm disorders [13 non‐24 hour sleep‐wake syndrome (non‐24), 76 delayed sleep phase syndrome (DSPS), 11 irregular sleep‐wake pattern (irregular) and six long sleepers] were treated with vitamin B12, bright light, chronotherapy and/or hypnotics. These therapies caused moderate or remarkable improvement in 32% of the non‐24, 42% of DSPS, 45% of irregular and 67% of long sleepers. A lack of adequate sleep, unpleasant feelings at waking and daytime drowsiness were also improved in DSPS.
Biomedical ambivalence: Asthma diagnosis, the pharmaceutical, and other contradictions in Barbados
Authors: WHITMARSH IAN 
Published: March 2008

ABSTRACTIn recent years in Barbados, the interaction of multinational pharmaceutical companies, the Ministry of Health (MOH), and international biomedical research has resulted in a focus on pharmaceuticals in public health intervention and the production of an expansive category of asthma. This article explores the views and uses of this process based on fieldwork conducted with doctors, nurses, pharmacists, MOH officials, and patient families involved in asthma care. Following ambiguities and contradictions in the significance of biomedical objects, I argue that this integration of pharmaceutical markets occurs with a foundational instability. Such ambiguity and contradiction are central to both the efficacy and undermining of global economic processes, including “pharmaceuticalization.”[pharmaceuticalization, ambiguity, asthma, globalization]
The work of the present: Constructing messianic temporality in the wake of failed prophecy among Chabad Hasidim
Authors: KRAVEL‐TOVI MICHAL , BILU YORAM 
Published: March 2008

ABSTRACTTemporal issues have remained relatively unelaborated in the rich body of research that applies cognitive dissonance theory to millenarian movements following a failed prophecy. We engage these issues by exploring how themeshichistim(messianists) among the Jewish ultraorthodox Chabad (Lubavitch) Hasidim employ temporal categories to deal with the crisis entailed in the death of their leader, the expected Messiah. In messianic Chabad, a double‐edged “work of the present” has continued to evolve, simultaneously obfuscating and accentuating temporal delineations between past, present, and future. The ensuing dialectical reality puts into question the common notion that millenarian movements such as Chabad strive at all costs to restore the balance disrupted by failed prophecy. [millenarian movements, messianic temporality, cognitive dissonance, Chabad‐Lubavitch]
Patriarchy through lamentation in Azerbaijan
Authors: GOLUBOFF SASCHA L. 
Published: March 2008

ABSTRACTIn this article, I analyze patriarchy through the lens of emotional discourse in and beyond death rituals among Mountain Jews in northeastern Azerbaijan. I argue that the time‐bound nature of female lamentation and the recent development of a popular narrative conceptualizing this genre as the custom defining Mountain Jewish identity in the Caucasus ultimately work to disempower women, reaffirming gender roles through narratives of suffering. Even though they use lamentations to address grievances within a context of increased outward migration, Mountain Jewish women cannot easily escape the conservative force that sorrow plays in their daily and ritual lives. [Mountain Jews, Azerbaijan, death, feminist ethnography, emotion, women, mourning]
Atomoxetine Increases Histamine Release and Improves Learning Deficits in an Animal Model of Attention‐Deficit Hyperactivity Disorder: The Spontaneously Hypertensive Rat
Authors: Liu Li‐Li , Yang Jie , Lei Ge‐Fei , Wang Gui‐Ju , Wang Yu‐Wei , Sun Ruo‐Peng 
Published: March 2008

Abstract: Substantial development in the pharmacological treatment for attention‐deficit hyperactivity disorder (ADHD) has been made recently including approval of new non‐stimulant agents targeting noradrenergic, histaminergic and dopaminergic systems. Among such, atomoxetine has been widely used, although its mechanism of action is poorly understood. It is known that central nervous system histamine is closely associated with cognition and it was recently shown that both atomoxetine and methylphenidate enhance cortical histamine release in rats. To that end, the aim of our study was to investigate the effect of atomoxetine (2 mg/kg, intraperitoneally) on histamine release using the microdialysis technique in the spontaneously hypertensive rat (SHR), a suitable genetic model for ADHD. Our data confirmed that atomoxetine increases extracellular levels of histamine in the prefrontal cortex, a brain region that is implicated in the pathophysiology of ADHD. Given the tie between histamine neurotransmission and treatment of cognitive dysfunction, we also assessed the effects of atomoxetine on learning and memory as measured by the Morris water maze in SHR. The results indicated that atomoxetine significantly ameliorated performance in the Morris water maze, consistent with its histamine‐enhancing profile. In conclusion, the current study provides further support for the notion that the therapeutic effect of atomoxetine could involve activation of histamine neurotransmission within the prefrontal cortex.
Pharmacologic Effects of Ospemifene in Rhesus Macaques: A Pilot Study
Authors: Wurz Gregory T. , Hellmann‐Blumberg Utha , DeGregorio Michael W. 
Published: March 2008

Abstract:  Ospemifene (Ophena™) is a new selective oestrogen receptor modulator currently in phase III clinical development for treatment of post‐menopausal vulvar and vaginal atrophy. In the present study, we examined the pharmacokinetics, toxicity, and DNA adduct forming potential of ospemifene in the liver and endometrium of rhesus macaques following single and subchronic dosing schedules to better understand the potential toxicologic effects of ospemifene. During single weekly dosing, six macaques were administered 35 mg/kg/week ospemifene orally for 3 weeks. Pharmacokinetics, haematologic toxicity, uterotrophic effects and serum cholesterol levels were monitored. Additionally, two animals were subchronically dosed with 60 mg ospemifene for 9 weeks, followed by 12 mg/day for 3 weeks. Serum cholesterol and pharmacokinetics were monitored, and serial liver and endometrial biopsies were collected during and after treatment to evaluate DNA adduct formation. Following single weekly dosing, no significant haematologic toxicities or uterotrophic effects associated with ospemifene were observed. Peak absorption was 4–5 hr, and the elimination half‐life was approximately 22 hr. Serum low‐density lipoprotein and triglyceride levels trended lower while no other effects on serum lipids were observed. Subchronic dosing resulted in no haematologic toxicity, a lowering of low‐density lipoprotein and triglyceride levels, and an increase in high‐density lipoprotein levels that were reversed following cessation of dosing. No clinically relevant uterine or endometrial effects were observed, and no DNA adducts were detected in the liver or endometrial biopsies. The results of our pilot study show that ospemifene may lack genotoxic and toxic effects while having a favourable pharmacokinetic profile.
AMPK inactivation in mononuclear cells: a potential intracellular mechanism for exercise-induced immunosuppression
Authors: Moir Hannah , Butcher Lee , Jones Ken P. , Hughes Michael G. , Neale Huw , Jia Huidong , Al-Ismaily Zuleikha , Webb Richard 
Published: March 2008

There is much evidence that prolonged intense exercise suppresses the immune system. However, the intracellular biochemical mechanisms linking exercise and immunosuppression remain obscure. The purpose of this study was to investigate the hypothesis that exercise-induced inactivation of 5′AMP-activated protein kinase (AMPK) disrupts individual immune cell function, and thus may be linked to exercise-induced immunosuppression. To confirm AMPK’s role in immune cells, AMPK activity was assessed in cultured monocytic Mono Mac 6 (MM6) cells. The effects of single bouts of intense exercise (45 min cycling; 70% VO2 max) on several immune parameters including mononuclear cell AMPK phosphorylation were investigated in 10 male volunteers. In vitro, the mitochondrial ATP synthase inhibitor oligomycin brought about transient decreases in cellular [ATP] (0.41 ± 0.04 pmol/cell to 0.31 ± 0.02 pmol/cell), and activation of AMPKα1 (170.7% ± 31.2% basal) and the glycolytic enzyme inducible phosphofructokinase 2 (iPFK-2) (225.0% ± 46.1% basal), with the latter effects coinciding with recovery from ATP depletion. In contrast, exercise-induced transient (~1 h) decreases in AMPKα1 phosphorylation (64.4% ± 17.6% basal). This AMPK inactivation coincided with comparable transient decreases in other immune parameters (salivary IgA levels, serum cytokine levels, monocyte CD36 expression). Although the brief exercise bout employed here is not sufficient to cause full-fledged immunosuppression, exercise-induced transient decreases in mononuclear cell AMPK activation (as seen in this study) may cause energy depletion within individual immune cells, and therefore have an impact upon their ability to carry out their functions. Thus, we suggest that prolonged, repeated, high-intensity exercise that leads to clinically relevant immunosuppression may do so via AMPK inactivation within immune cells.
Effect of dietary protein content during recovery from high-intensity cycling on subsequent performance and markers of stress, inflammation, and muscle damage in well-trained men
Authors: Rowlands David S. , Rössler Karin , Thorp Rhys M. , Graham David F. , Timmons Brian W. , Stannard Stephen R. , Tarnopolsky Mark A. 
Published: March 2008

Nutrition is an important aspect of recuperation for athletes during multi-day competition or hard training. Post-exercise carbohydrate is likely to improve recovery, but the effect of protein is equivocal. The objective of this study was to determine the effect of post-exercise dietary protein content imposed over a high-carbohydrate background on subsequent performance. Using a crossover design, 12 cyclists completed 3 high-intensity rides over 4 days. Day 1 comprised 2.5 h intervals, followed by repeat-sprint performance tests on days 2 (15 h post) and 4 (60 h post), interspersed with a rest day. During 4 h recovery on days 1 and 2, cyclists ingested either 1.4 g·kg–1·h–1 carbohydrate, 0.7 g·kg–1·h–1 protein and 0.26 g·kg–1·h–1 fat (protein-enriched) or 2.1 g·kg–1·h–1 carbohydrate, 0.1 g·kg–1·h–1 protein, and equal fat (control). At other times, cyclists ingested a standardized high-carbohydrate diet. Anabolism was gauged indirectly by nitrogen balance, stress and inflammation via cortisol and cytokines, skeletal-muscle membrane disruption by creatine kinase, and oxidative stress by malonyl dealdehyde. Sprint mean power was not clearly different on day 2 (0.0%; 95%CL: ±3.9%), but on day 4 it was 4.1% higher (±4.1%) in the protein-enriched condition relative to control. Reduced creatine kinase was possible (26%; ±30%) but effects on oxidative stress, inflammatory markers, and cortisol were inconclusive or trivial. Overnight nitrogen balance was positive in the protein-enriched condition on day 1 (249 ± 70 mg N·kg FFM–1; mean ± SD), but negative (–48 ± 26 mg N·kg FFM–1) in the control condition. A nutritive effect of post-exercise protein content was not discernible short term (15 h), but a delayed performance benefit (60 h) was observed following protein-enriched high-carbohydrate ingestion.
The role of protein-mediated transport in regulating mitochondrial long-chain fatty acid oxidation
Authors: Holloway Graham Paul 
Published: March 2008

This thesis is an investigation of the role of fatty acid translocase (FAT/CD36), plasma membrane associated fatty acid binding protein (FABPpm), and carnitine palmitoyltransferase I (CPTI) in transporting long-chain fatty acids (LCFAs) across mitochondrial membranes. Maximal CPTI activity, as well as the sensitivity of CPTI for its substrate palmitoyl-CoA (P-CoA) and its inhibitor malonyl-CoA (M-CoA), were measured in mitochondria isolated from human vastus lateralis muscles at rest and following muscle contraction. Exercise did not alter maximal CPTI activity or the sensitivity of CPTI for P-CoA. In contrast, exercise progressively attenuated the ability of M-CoA to inhibit CPTI activity. Mitochondrial FAT/CD36 protein content was also measured at rest, during, and following 2 h of cycling at ~60% maximal oxygen uptake. Exercise progressively increased the content of mitochondrial FAT/CD36 (+59%), which was significantly (p < 0.05) correlated with palmitate oxidation during exercise (r = 0.52), while palmitate oxidation was inhibited ~80% by the administration of a specific FAT/CD36 inhibitor. These data suggest that alterations in CPTI M-CoA sensitivity and increases in mitochondrial FAT/CD36 coordinate exercise-induced increases in fatty acid oxidation. FABPpm, another plasma membrane transport protein, has identical amino acid sequence to mitochondrial aspartate aminotransferase (mAspAT). Since FABPpm contributes to plasma membrane fatty acid transport, the role of FABPpm with respect to mitochondrial LCFA transport was investigated. However, unlike FAT/CD36, muscle contraction did not induce an increase in mitochondrial FABPpm protein in rat or human skeletal muscle. In addition, electrotransfecting FABPpm cDNA into rat skeletal muscle upregulated this protein in mitochondria by 80% without altering mitochondrial palmitate oxidation. In contrast, electrotransfection increased mAspAT activity by 90%, and this was correlated (r = 0.75; p < 0.01) with FABPpm protein. These data suggest that FABPpm does not contribute to the regulation of mitochondrial LCFA transport. Previously, it has been suggested that mitochondria from obese individuals contain an inherent dysfunction to oxidize LCFAs. In age-matched lean (BMI = 23.3 ± 0.7 kg·m–2) and obese (BMI = 37.6 ± 2.2 kg·m–2) individuals, isolated mitochondrial palmitate oxidation was not altered. In addition, mitochondrial FAT/CD36 content was not different in lean and obese individuals. In contrast, citrate synthase and β-hydroxyacyl-CoA dehydrogenase, common markers of total mitochondrial content, were decreased with obesity. Therefore, the decrease in mitochondrial content appeared to account for the observed reductions in whole-muscle LCFA oxidation.
Determinants ofVO2 maxdecline with aging: an integrated perspective
Authors: Betik Andrew C. , Hepple Russell T. 
Published: March 2008

Aging is associated with a progressive decline in the capacity for physical activity. Central to this decline is a reduction in the maximal rate of oxygen utilization, or VO2 max. This critical perspective examines the roles played by the factors that determine the rate of muscle oxygen delivery versus those that determine the utilization of oxygen by muscle as a means of probing the reasons for VO2 maxdecline with aging. Reductions in muscle oxygen delivery, principally due to reduced cardiac output and perhaps also a maldistribution of cardiac output, appear to play the dominant role up until late middle age. On the other hand, there is a decline in skeletal muscle oxidative capacity with aging, due in part to mitochondrial dysfunction, which appears to play a particularly important role in extreme old age (senescence) where skeletal muscle VO2 maxis observed to decline by approximately 50% even under conditions of similar oxygen delivery as young adult muscle. It is noteworthy that at least the structural aspects of the capillary bed do not appear to be reduced in a manner that would compromise the capacity for muscle oxygen diffusion even in senescence.
Radiation Enhances Adenoviral Gene Therapy in Pancreatic Cancer via Activation of Cytomegalovirus Promoter and Increased Adenovirus Uptake
Authors: Egami Takuya , Ohuchida Kenoki , Mizumoto Kazuhiro , Onimaru Manabu , Toma Hiroki , Nishio Shoko , Nagai Eishi , Matsumoto Kunio , Nakamura Toshikazu , Tanaka Masao 
Published: March 2008

Abstract
Purpose: Adenovirus-mediated gene therapy combined with radiation is expected to be a new approach to treat pancreatic cancer. However, there are no reports of definitive effects of radiation on adenovirus-mediated gene therapies. In the present study, we investigated the effect of radiation on the transduction efficiency of an adenovirus-based gene therapy.
Experimental Design: We used adenovirus expressing NK4 (Ad-NK4), an antagonist for hepatocyte growth factor, as a representative gene therapy. Pancreatic cancer cells preinfected with Ad-NK4 were irradiated, and NK4 levels in culture media of these cells were measured. We investigated cytomegalovirus (CMV) promoter activity and uptake of adenovirus in these cells. To examine the effect of radiation in vivo, Ad-NK4 was given to irradiated subcutaneous tumors in nude mice, and NK4 levels in tumors were measured.
Results: NK4 levels in culture media of irradiated cells were 4.5-fold (P &lt; 0.01) higher than those of nonirradiated cells. Radiation enhanced activation of the CMV promoter and adenovirus uptake (P &lt; 0.01), leading to increased levels of NK4. We found that activation of p38 mitogen-activated protein kinase and up-regulation of dynamin 2 may be involved in the radiation-induced activation of the CMV promoter and adenovirus uptake, respectively. NK4 levels in irradiated tumors were 5.8-fold (P = 0.017) higher than those in nonirradiated tumors.
Conclusions: The present findings suggest that radiation significantly improves the efficiency of adenovirus-mediated gene transfer in pancreatic cancer and probably contributes to decreasing the dose of adenovirus required for gene transfer and controlling side effects of adenovirus infection in nonirradiated normal tissue.
Antimyeloma Effects of a Sesquiterpene Lactone Parthenolide
Authors: Suvannasankha Attaya , Crean Colin D. , Shanmugam Rajasubramaniam , Farag Sherif S. , Abonour Rafat , Boswell H. Scott , Nakshatri Harikrishna 
Published: March 2008

AbstractPurpose: Nuclear factor-κB (NF-κB), activated in multiple myeloma (MM) cells by microenvironmental cues, confers resistance to apoptosis. The sesquiterpene lactone parthenolide targets NF-κB. However, its therapeutic potential in MM is not known.Experimental Designs: We explored the effects of parthenolide on MM cells in the context of the bone marrow microenvironment.Results: Parthenolide inhibited growth of MM cells lines, including drug-resistant cell lines, and primary cells in a dose-dependent manner. Parthenolide overcame the proliferative effects of cytokines interleukin-6 and insulin-like growth factor I, whereas the adhesion of MM cells to bone marrow stromal cells partially protected MM cells against parthenolide effect. In addition, parthenolide blocked interleukin-6 secretion from bone marrow stromal cells triggered by the adhesion of MM cells. Parthenolide cytotoxicity is both caspase-dependent and caspase-independent. Parthenolide rapidly induced caspase activation and cleavage of PARP, MCL-1, X-linked inhibitor of apoptosis protein, and BID. Parthenolide rapidly down-regulated cellular FADD-like IL-1β–converting enzyme inhibitory protein, and direct targeting of cellular FADD-like IL-1β–converting enzyme inhibitory protein using small interfering RNA oligonucleotides inhibited MM cell growth and lowered the parthenolide concentration required for growth inhibition. An additive effect and synergy were observed when parthenolide was combined with dexamethasone and TNF-related apoptosis-inducing ligand, respectively.Conclusion: Collectively, parthenolide has multifaceted antitumor effects toward both MM cells and the bone marrow microenvironment. Our data support the clinical development of parthenolide in MM therapy.
Synergistic Antipancreatic Tumor Effect by Simultaneously Targeting Hypoxic Cancer Cells With HSP90 Inhibitor and Glycolysis Inhibitor
Authors: Cao Xianhua , Bloomston Mark , Zhang Tao , Frankel Wendy L. , Jia Guang , Wang Bing , Hall Nathan C. , Koch Regina M. , Cheng Hao , Knopp Michael V. , Sun Duxin 
Published: March 2008

AbstractPurpose: We sought to examine the synergistic antipancreatic cancer effect by simultaneously targeting hypoxic cancer cells with heat-shock protein 90 (HSP90) inhibitor and blockade of energy production.Experimental Design: The anticancer effects of an HSP90 inhibitor (geldanamycin) in pancreatic cells were investigated in hypoxia and normoxia. A hexokinase II inhibitor, 3-broma-pyruvate (3BrPA), was evaluated for selective glycolysis inhibition in hypoxia as a sensitizer of HSP90 inhibitor against pancreatic cancer. The HSP90 client protein degradation was monitored by Western blot. The synergistic antitumor effect of geldanamycin and 3BrPA was evaluated in a xenograft pancreatic cancer model and monitored by a noninvasive dynamic contrast-enhanced magnetic resonance imaging.Results: Hypoxia enhanced HIF-1α expression by 11-fold in pancreatic cancer cells, and HSP90 inhibitor exhibited a seven- to eightfold higher anticancer effect in hypoxia compared with normoxia via HSP90 client protein degradation. 3BrPA selectively inhibited glycolysis and sensitized geldanamycin against pancreatic cancer cells by 17- to 400-fold through HSP90 client protein degradation. The synergistic anticancer effect of reduced doses of geldanamycin and 3-BrPA was confirmed in xenograft models in vivo by more than 75% tumor growth inhibition.Conclusions: The combination of HSP90 inhibitors and glycolysis inhibitors provides preferential inhibition of cancer cells in hypoxia through HSP90 client protein degradation and selective glycolysis inhibition. This may provide a new therapeutic regimen to battle chemotherapy-resistant pancreatic cancers, by enhancing the synergistic therapeutic efficacy and reducing dose-limiting toxicity.
Molecular Alterations in Spontaneous Sputum of Cancer-Free Heavy Smokers: Results from a Large Screening Program
Authors: Baryshnikova Ekaterina , Destro Annarita , Infante Maurizio Valentino , Cavuto Silvio , Cariboni Umberto , Alloisio Marco , Ceresoli Giovanni Luca , Lutman Romano , Brambilla Giorgio , Chiesa Giuseppe , Ravasi Gianni , Roncalli Massimo 
Published: March 2008

Abstract
Purpose: The high mortality rate for lung cancer is likely to be reduced by the development of a panel of sensitive biological markers able to identify early-stage lung cancers or subjects at high risk. The aim of this study was to establish the frequency of K-ras and p53 mutations and p16INK4A, RASSF1A, and NORE1A hypermethylation in sputum of a large cohort of cancer-free heavy smokers and to assess whether these markers are suitable for a routine use in the clinical practice for the early diagnosis of pulmonary cancer.
Experimental Design: Sputum samples were collected from 820 heavy smokers. Inclusion criteria consisted of radiologic and cytologic absence of pulmonary lesions, age at least 60 years, male gender, and a smoking history of at least 20 pack-years.
Results: The analysis identified 56 individuals (6.9%) with one molecular alteration. p53 mutation and p16INK4A, RASSF1A, and NORE1A methylation frequencies were 1.9%, 5.1%, 0.8%, and 1.0%, respectively; no K-ras mutations were found. One patient with p53 mutations was diagnosed with an early-stage lung cancer after 3-years of follow-up. The molecular analysis of bronchoscopy samples confirmed in half of the cases alterations present in sputum without revealing additional molecular changes.
Conclusions: Genetic and epigenetic abnormalities can be detected in cancer-free heavy smokers. Although the predictive value of the cancer risk is still to be established as it requires not less than 5 years of follow-up, p53 and p16INK4A are more promising candidates than K-ras, RASSF1A, and NORE1A for the pulmonary molecular screening of heavy smokers healthy individuals.