bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical characteristics of Tourette syndrome
Authors: KANO YUKIKO , OHTA MASATAKA , NAGAI YOKO
Published: March 2008

Abstract The aim of the present study was to examine the clinical characteristics of Tourette syndrome (TS) in terms of symptomatology, outcome and organic and genetic factors, and to compare these with results of previous studies on TS in Western countries and in Japan, on the basis of precise information taken from a large number of TS patients under psychiatric treatment in Japan. There was a total of 64 TS patients (55 males and nine females) selected from those who visited our outpatient clinic from 1974 to 1993 and were found to meet the criteria for Tourette's disorder of DSM‐III‐R. The mean patient age at entry to the present study was 17.4 years (SD:7.2). All data were collected through a systematic chart review of subjects, including data on tic symptoms and the course of their development; complications and developmental histories; family histories; medical and psychological examinations; treatment; severity and outcome. A check of the data showed that the mean age at onset was 6.9 years (SD:2.7). An analysis of the progression of the symptoms revealed that ‘generalized tics’ afflicting the entire body were found in 64.1% of subjects and coprolalia was found in 50%. The main complications were obsessive‐compulsive symptoms (OCS) in 62.5% of patients and attention deficit hyperactivity disorder (ADHD) in 17.2%. Of their parents, 7.0% had tic disorders except TS and 1.6% had TS. Contrary to results from previous studies of TS, our study revealed that at least the incidence of coprolalia in TS patients in Japan is not lower than in Western countries. However, the frequency of familial cases seemed to be lower than previously reported for Western patients. Outcome was fairly related with ‘generalized tics,’ OCS, aggressiveness and ADHD.
Symbolic meanings of island in dreams
Authors: TAKAO HIROYUKI
Published: March 2008

Abstract Six dreams reported from neurotic patients in the therapy of Jungian analysis are presented to illustrate the symbolic meanings of islands in dreams. The island in dreams symbolizes (i) the entrance point into Jungian analysis, (ii) a complex in which a dreamer has got involved and (iii) the beginning of the newly organized ego consciousness. The multiple meanings of islands are suggested to originate from several levels of the unconscious from which the identical symbol of island comes from.
Prevalence of use of medically prescribed hypnotics among adult Japanese women in urban residential areas
Authors: KAGEYAMA TAKAYUKI , KABUTO MICHINORI , NITTA HIROSHI , KUROKAWA YOSHIKA , TAIRA KAZUHIKO , SUZUKI SHOSUKE , TAKEMOTO TAI‐ICHIRO
Published: March 2008

AbstractBased on a population survey on insomnia among 3600 adult Japanese women living in urban areas, the prevalence of use of medically prescribed hypnotics is determined. The prevalence of use of medically prescribed hypnotics increases with an increase in age (<1.0% for those aged 49 or younger, while 14.3% for those aged 70 or older), in agreement with the results reported in many Western nations. The current sleep disturbance is mild in nearly half of these hypnotics users. More than one‐third of the hypnotic users are receiving health care not for sleep problems but for depression, anxiety, or other reasons. More than one‐third of the hypnotic users are found to be receiving hypnotics from non‐psychiatrists. The percentage of this group is particularly high among those aged 60 or over, probably reflecting the fact that they are often consulting physicians for physical reasons. On the other hand, more than 80% of insomniacs are suggested to be untreated. Future public health research should focus on the quality of life and health care behaviors of untreated insomniacs and hypnotic users, especially among the elderly people, in order to assess the need for primary health care to prevent accidents, mortality, and psychiatric disorders related to sleep problems.
Prognosis of the middle‐aged and aged patients with obstructive sleep apnea syndrome
Authors: NODA AKIKO , OKADA TAMOTSU , YASUMA FUMIHIKO , SOBUE TOSHIKAZU , NAKASHIMA NOBUO , YOKOTA MITSUHIRO
Published: March 2008

Abstract The long‐term natural course of obstructive sleep apnea syndrome (OSAS) is studied in order to determine whether severity of nocturnal oxygen desaturation associated with apnea/hypopnea, body mass index (BMI), and hypertension influence survival in young (<40 years), middle‐aged (40–64 years), and aged (65 years) using a questionnaire survey. One hundred and forty‐eight patients with OSAS aged 17–78 years (136 men, 12 women, mean 52.0±12.3 yean), who were diagnosed by standard polysomnography (PSG) between 1983 and 1993, participated in the study. The survey revealed 15 deaths and 101 survivors; 32 subjects could not be located. The survival rate was 71.4% (95% confidence interval:55.6–87.2%). The survival rate in patients with OSAS was significantly lower than that in the age and sex‐adjusted control Japanese population (87.6%). In the young group, only one death (a 19–year‐old woman) occurred unexpectedly during sleep. The patient showed an apnea/hypopnea index (AHI) of 33 per h and the length of time that the nocturnal oxygen saturation (SaO2) fell below 90% (time of SaO2 < 90%) of 205 min. The survival rate in middle‐aged patients with OSAS was significantly lower than that in the age and sex‐adjusted control Japanese population (79.2 vs 91.0%), but this pattern was not seen among the aged. Time of SaO2 <90% was significantly longer in the middle‐aged patients than in the aged patients, but AHI did not differ between the two groups. Moreover, it was significantly correlated with AHI in middle‐aged patients, but not in the aged patients. The survival rate was significantly lower in patients with hypertension than in the patients without such complications in the middle‐aged group (57.9 vs 90.4%). Cox proportional‐hazard regression model including age, hypertension, BMI, AHI, lowest SaO2, and time of SaO2 <90% showed that hypertension was only significantly associated with lower survival rate in total group and middle‐aged patients, but not in the young or aged patients. The prognosis in patients with OSAS may differ among the generations. The prognosis in the middle‐aged population may depend on the role of OSAS on the complications of hypertension or severity of oxygen desaturation, but not on AHI only.
Hypogammaglobulinemia during antipsychotic therapy
Authors: ABE SHUZO , SUZUKI TOSHIHITO , HORI TAKAFUMI , BABA ATSUOMI , SHIRAISHI HIROYASU
Published: March 2008

Abstract Hypogammaglobulinemia in a 22‐year‐old woman with brief psychotic disorder developed during antipsychotic therapy. Severe decreases in immunoglobulin IgM, IgG, and IgA concentration in serum were observed 4 months after the treatment with chlorpromazine (CPZ) and the other types of antipsychotics. Neither physical diseases nor family history for immunological disturbances was seen. No clinical symptoms in relation to immunological disturbances (i.e. infectious disease), were noted. Gammaglobulin levels in serum returned to a normal range after a replacement of chlorpromazine to timiperone. The hypogammaglobulinemia in the present case was considered to be due to the inhibition of gammaglobulin synthesis by CPZ.
Effects of daytime activity upon the timing of REM sleep periods during a night
Authors: KOBAYASHI TOSHINORI , ISHIKAWA TOHRU , ARAKAWA KAZUNARI
Published: March 2008

Abstract The effects of mental and physical daytime activities upon REM sleep cycle (REM cycle) during 1 night was studied in five university students (aged 19–25 years). Mental activity with high tension has effects upon the timing of REM sleep periods in the later part of the night. Physical activity has effects upon the timing of REM sleep in the early part of the night. The result suggests that mental and/or physical activities during daytime modulate REM cycle during the night.
Bifurcation properties of the two process model
Authors: NAKAO MITSUYUKI , YAMAMOTO MITSUAKI
Published: March 2008

Abstract Daan's two process model is known to be one of the most powerful models, covering various situations from free‐running to sleep deprivation. In this study, bifurcation properties of the model dynamics as function of a gap, D, between the threshold processes are clarified using a circle map. As a function of D, we will show that the model has the different types of the mutual entrainment regions that are intervened by the tangent bifurcation. The variable behavior of human circadian rhythm is suggested to be systematically understood based on the bifurcation properties of the two process model.
Effects of the timing of exercise on the night sleep
Authors: YOSHIDA HIRONORI , ISHIKAWA TOHRU , SHIRAISHI FUMIO , KOBAYASHI TOSHINORI
Published: March 2008

Abstract The effects of physical exercises taken at different times in the day upon subjective sleep feeling were examined in five healthy university students (aged 20–22 years); morning exercise, evening exercise, and late evening exercise. The late evening exercise with the strength of 50–60% VO2max of 1 h has the effect of getting better subjective sleep feeling in the morning and the effect of the decreased daytime sleepiness.
Cortical activity of REM sleep often occurs earlier than other physiological phenomena
Authors: NIIYAMA YOSHITSUGU , SERINE ATSUSI , FUSHIMI MASAHITO , HISHIKAWA YASUO
Published: March 2008

Abstract N300 appearing in response to sound stimulus was used as an index to determine the occurrence of cortical activity characterizing REM sleep. In 5/10 subjects, marked reduction of N300 amplitude occurred even in the period of 0.5‐2.5 min immediately preceding the appearance of muscle atonia characterizing REM sleep. Neither muscle atonia nor rapid eye movements appeared prior to the marked reduction of N300 amplitude in any subject. This suggests that the cortical activity characterizing REM sleep sometimes occurs a few minutes (or less) earlier than other physiological phenomena.
Observational assessment of patients' sleep complaints in the coronary care unit
Authors: MITAMURA SUGUMI , NAKAMURA MAYUMI , YAMAMOTO TAKAHO , UCHIYAMA MAKOTO
Published: March 2008

Abstract Sleep‐wake disorders are common in patients who are treated in coronary care units (CCU). We report a clinical trial aimed at developing an observational assessment of patients' sleep complaints in a CCU. Thirty‐four inpatients with coronary heart diseases in the CCU (Tokyo Metropolitan Hiroo General Hospital) participated in the study. The patient's sleep state was assessed by nursing staff and classified as wakefulness, drowsy and asleep according to a semi‐structured observation. Subjective sleep feelings upon rising was also investigated. Sleep disruptions during the latter half of the night was found to be an important determining factor of sleep feeling upon rising.
Effects of volitional lifestyle on sleep‐life habits in the aged
Authors: SHIROTA AI , TANAKA HIDEKI , HAYASHI MITSUO , HORI TADAO
Published: March 2008

Abstract This study investigates the relationship between a volitional lifestyle and sleep‐life habits in the aged. High volitional group (HVG:n= 45, 26 men and 19 women, mean age 73.0 years) and low‐volitional group (LVG:n= 45, 27 men and 18 women, mean age 72.2 years) were grouped using the scale of self‐confidence. It was found that high volitional aged individuals had a relatively well structured sleep, and that most had become accustomed to taking an appetitive nap (an individual with a mean wake time shorter than the average) in the mid‐afternoon without experiencing insomniac problems.
Gender differences in the sleep of middle‐aged individuals
Authors: KOBAYASHI RIKO , KOHSAKA MASAKO , FUKUDA NORIKO , HONMA HIROSHI , SAKAKIBARA SATOSHI , KOYAMA TSUKASA
Published: March 2008

Abstract The study was designed to investigate gender differences in the sleep‐wake patterns of healthy middle‐aged individuals in their home environment. Polysomnography showed that daytime napping was more common in men than in women. Men had lower sleep efficiency index and experienced more stage 1 sleep. Males had significantly less stages 3 + 4 sleep, less stage REM sleep, and more transitions to wake from REM sleep. Men could not maintain stage REM as well as women. This study indicates that the gender differences in the sleep‐wake patterns have appeared in a group of middle‐aged individuals.
Relationship between nocturnal urinary frequency and sleep disturbances in aged men
Authors: TANAKA YOSHIYUKI , KAWAUCHI AKIHIRO , WATANABE HIROKI , IMADA NAOKI
Published: March 2008

Abstract The relationship between nocturnal urinary frequency and sleep disturbances is investigated in aged men in 12 rural towns in Kyoto and Shiga Prefectures. The subjects were 178 men who did not have diseases or symptoms that were likely to affect urinary condition or sleep. There were no significant differences in sleep disturbances, except sleep maintenance, between the normal group (nocturnal urinary frequency below twice per night) and the abnormal group (nocturnal urinary frequency twice or more per night). In healthy aged men, nocturnal urinary frequency only caused disturbance in sleep maintenance, but did not cause any other sleep disturbance.
Sleep improvement by light in a demented aged individual
Authors: OKUMOTO YOSHIHIR.O , KOYAMA EMI , MATSUBARA HOZUMI , NAKANO TOSHIO , NAKAMURA REIZO
Published: March 2008

Abstract We administered daily morning bright light exposure in two separate periods to a demented aged subject in a nursing home and analyzed the sleep pattern changes from the sleep diary over 6 months. In the first light exposure period, the ratio of sleep time in night hours increased and maintained a higher value throughout the period than the previous baseline. After stopping the light exposure, the sleep pattern of the subject deteriorated. Resuming the light exposure reproduced similar sleep pattern changes. These results suggest that morning bright light exposure provides a better environment for aged persons to maintain a regular sleep‐wake pattern.
Sleep behavior of pregnant women using sleep log
Authors: SUGIHARA KIYOMI , KOBAYASHI TOSHINORI
Published: March 2008

Abstract Sleep log study, which was designed to study sleep characteristics by questionnaire, was performed on 172 pregnant women about the relationship between their pregnancy and their night sleep. Sleep behavior by sleep log revealed that they woke more frequently during the course of their pregnancy and that their total sleep time decreased gradually toward the end of their pregnancy. According to their subjective evaluations, these shortages of night sleep could not be made up with the morning naps in the multiparas as was the case of the primiparas. These changes in sleep characteristics have been studied from biological, psychological and social factors view points.
Differences in arousal response between aged and middle‐aged patients with obstructive sleep apnea syndrome
Authors: OKADA TAMOTSU , HANYU MIKA , NODA AKIKO , KAYUKAWA YUHEI , OHTA TATSURO
Published: March 2008

Abstract The aim of this study is to show the clinical significance of the differences in arousal response at a termination of apnea/hypopnea between aged and middle‐aged patients with obstructive sleep apnea syndrome (OSAS). We polygraphically assessed electrocardiographic (ECG) and electroencephalographic (EEG) arousal. Electrocardiographic arousal was defined as an abrupt increase in heart rate at a termination of apnea/hypopnea. Our findings showed that EEG and ECG arousal at a termination of apnea/hypopnea were significantly suppressed in aged patients with OSAS, which might provide useful information on the pathophysiology of OSAS.
Daytime sleepiness and automobile accidents in patients with obstructive sleep apnea syndrome
Authors: NODA AKIKO , YAGI TOMOKO , YOKOTA MITSUHIRO , KAYUKAWA YUHEI , OHTA TATSURO , OKADA TAMOTSU
Published: March 2008

Abstract We evaluated the rate of automobile accidents and daytime sleepiness using the Epworth sleepiness scale (ESS) in 44 patients with obstructive sleep apnea syndrome (OSAS). We defined the automobile accident score as a sum of two points for every one automobile accident and one point for every near‐miss accident. Automobile accidents and near‐misses were found in 54.5% and 50.0% in patients with OSAS. Automobile accident score was significantly correlated with the ESS score (r= 0.56, P < 0.01). Our findings suggest that ESS score may be useful in detecting patients with the potential risk of automobile accidents associated with daytime sleepiness.
Circadian rhythms of hormone concentrations in alcohol withdrawal
Authors: MUKAI MASAKI , UCHIMURA NAOHISA , HIRANO TAKASHI , OHSHIMA HIROHARU , OHSHIMA MASACHIKA , NAKAMURA JUN
Published: March 2008

Abstract We investigated the circadian rhythm of hormones (Cortisol, melatonin) in alcoholic patients during and 1 month after alcohol withdrawal. Patients with delirium tremens had irregular serum hormone concentration rhythms during withdrawal, which normalized after the withdrawal period. Patients without delirium tremens had normal circadian rhythms even during the withdrawal period. We speculated that the disturbance of the biological oscillator, in terms of the decline of synchronizing function or the decrease in synchronizing factors, caused abnormal circadian rhythms of hormone release during delirium tremens.
Effects of the gradually increasing dawn light stimulation on sleep feeling
Authors: ARAKAWA KAZUSHIGE , SHIRAKAWA SHUICHIROH , KOBAYASHI TOSHINORI , OGURI MITSUGU , KAMEI YUICHI , TUMURA AND TOYOAKI
Published: March 2008

Abstract Effects of a new lighting stimulation system upon subjective sleep and waking feeling were psychophysiologically examined in 24 healthy students in order to develop a way of obtaining comfortable awakening. The subjects underwent three different experimental conditions:the light stimulation condition, non‐light stimulation condition and the control condition. The satisfaction of sleep was higher and day sleepiness lower in the light condition compared with the other two conditions. Subjective fatigue related to mental functions at waking was also smaller in the light condition compared with the other two conditions. These results suggest that the improvement of sleep feeling and waking seems to be achieved by gradual increased dawn light stimulation.
Effects of short duration morning bright light in healthy elderly. II:Sleep and motor activity
Authors: KOHSAKA MASAKO , FUKUDA NORIKO , KOBAYASHI RIKO , HONMA HIROSHI , SAKAKIBARA SATOSHI , KOYAMA EMI , NAKANO OSHIO , MATSUBARA HOZUMI
Published: March 2008

Abstract Subjective sleep feelings and motor activity were measured in seven healthy elderly subjects for 6 days. The subjects were exposed to bright light (6000 lux) for 30 min in the morning or instructed to sit in front of a desktop lighting device without light. The average level of motor activity during the night was significantly decreased in the bright light condition, compared with the controlled condition. However, daytime motor activity did not show significant differences between the two conditions. From these findings, even a short duration of morning bright light is effective in maintaining sleep without changing daytime activity.
Melatonin treatment for rhythm disorder
Authors: KATO MASAAKI , KAJIMURA NAOFUMI , SEKIMOTO MASANORI , WATANABE TSUYOSHI , TAKAHASHI KIYOHISA
Published: March 2008

Abstract We tried melatonin treatment in two patients with non‐24 h sleep‐wake syndrome, who did not respond to treatments by vitamin B12, bright light therapy, or hypnotics. In one patient, melatonin 5–10 mg improved difficulty in falling asleep and in waking, although it failed to improve the sleep‐wake rhythm. In another patient, melatonin 3 mg successfully changed the sleep‐wake rhythm from free‐running pattern to delayed sleep phase pattern. However, melatonin re‐administration after a 4‐month drug‐free interval failed to improve his free‐running sleep‐wake rhythm. These results suggest that melatonin acted as a sleep inducer in one patient and as a phase setter in the other, although the effect on the latter patient was transient.
Spectral analysis of changes in electroencephalographic activity after the chewing of gum
Authors: MASUMOTO YASUHIRO , MORINUSHI TAKANOBU , KAWASAKI HIROTOKI , TAKIGAWA MORIKUNI
Published: March 2008

Abstract  The present study aimed to examine the psychosomatic effect in the chewing of marketed gum using eletroencephalogram (EEG) as an index. The EEG were taken in two sets: (i) a resting period before chewing (control recording) and a resting record (post‐resting recording) for examining reproducibility; and (ii) a control recording and resting period after gum‐chewing for 3 min (post‐chewing recording). The ratio of each frequency band to the total frequency power, the mean frequency of the alpha band and laterality of the frequency power was calculated. In the examination of the reproducibility, no statistically significant differences were observed between control recording and post‐resting recording in all indices. In the reflection of EEG after gum‐chewing, there were no significant differences between control recording and the post‐chewing recording. However, a significant interaction was observed among these indices by analysis of variance. In addition, the alpha power in the post‐chewing recording was significantly higher than that in the control recording at almost all the positions. In conclusion, the intra‐individual reproducibility of EEG was confirmed in the recording method. Furthermore, it was suggested that a significant interaction and a rising trend of the mean frequency of the alpha band after gum‐chewing reflected ‘arousal’ psychosomatic responses by the chewing of marketed gum.
Portfolio Selection and the Investment Performance of the UK Pension Funds*
Authors: SCOTT ANDREW , DINENIS ELIAS
Published: March 2008

Pension funds are the main institutional investors, accounting for 38 per cent of personal sector net financial wealth. As a result of their growing importance in mobilizing personal sector saving, they have emerged as the principal institutional investor, controlling over £200bn of funds at the end of 1987, their total net assets equalling 38 per cent of personal sector net financial wealth. Pension funds also dominate domestic asset markets, owning 27per cent of the stock of outstanding UK equity, 23 per cent of UK government securities and 17 per cent of total UK holdings of overseas equity. In this paper we present the conclusions from recent research, undertaken as part of an updating of the LBS Financial Model. Our results suggest that UK pension fund investment since 1980 is better than previous studies have suggested and, in particular, that funds outperformed the equity market in the 1980s, offering a higher return for any given level of risk. In addition fund behaviour is slow to change, with past behaviour exerting the strongest influence on current investment patterns. Fund managers also appear guilty of “short termism” in that they place little weight on events beyond the next three months. However, this has not made them inefficient. Finally, we find that actions to restrict the funds' surpluses should not affect their investment behaviour. Our results also suggest that the costs from exchange controls in the 1970s were substantial, amounting to some £4bn per year.
Focus: Supply‐Side Improvements in UK Exporting of Manufactures
Authors: HOLLY SEAN , WADE KEITH
Published: March 2008

The present difficulties with the UK current account deficit have breathed new life into longstanding doubts in some quarters about the fundamental state of UK manufacturing, despite the supply side reforms of the last ten years and the large increases in labour productivity. The deterioration in trade in manufactured goods from a small surplus of £2bn in 1982 to a deficit of £21bn in 1988, is taken to be the most stark illustration of this deep structural malaise.
Biomedical ambivalence: Asthma diagnosis, the pharmaceutical, and other contradictions in Barbados
Authors: WHITMARSH IAN
Published: March 2008

In 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

Temporal 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

In 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]
Deficiency in Cytosolic Malic Enzyme Does Not Increase Acetaminophen‐Induced Hepato‐Toxicity
Authors: Qian Su , Mumick Sheena , Nizner Peter , Tota Michael R. , Menetski Joseph , Reitman Marc L. , MacNeil Douglas J.
Published: March 2008

Abstract:  Cytosolic malic enzyme (ME‐1) is a nicotinamide adenine dinucleotide phosphate (NADP)‐dependent enzyme that generates NADPH. The activity of this enzyme, the reversible oxidative decarboxylation of malate to yield pyruvate, links glycolytic pathway to citric acid cycle. The high level of ME‐1 expression in liver, and its involvement in NADPH production, suggests reduced ME‐1 activity might compromise hepatic production of reduced glutathione (GSH) by the NADPH‐dependent enzyme glutathione reductase, and hence affect xenobiotic detoxification. The role of ME‐1 in liver detoxification was evaluated in Mod1 deficient mice (mod1−/–) by evaluating their sensitivity to acetaminophen‐induced liver injury. The results show that mod1−/– mice are not more sensitive to acetaminophen hepato‐toxicity. Although GSH levels were initially depleted more in the mod1−/– liver than in wild‐type controls, the GSH levels recovered quickly. In conclusion, our data indicate that ME‐1 deficiency does not adversely affect GSH‐dependent detoxification.
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.
Theaflavin‐3‐Gallate and Theaflavin‐3′‐Gallate, Polyphenols in Black Tea with Prooxidant Properties
Authors: Babich Harvey , Gottesman Reena T. , Liebling Emily J. , Schuck Alyssa G.
Published: March 2008

Abstract:  This study compared the in vitro responses of human gingival fibroblasts and of carcinoma cells derived from the tongue to theaflavin‐3‐gallate (TF‐2A) and theaflavin‐3′‐gallate (TF‐2B), polyphenols in black tea. The antiproliferative and cytotoxic effects of the theaflavin monomers were more pronounced to the carcinoma, than to the normal, cells. In phosphate buffer at pH 7.4, the theaflavins generated hydrogen peroxide and the superoxide anion, suggesting that their mode of toxicity may be due, in part, to the induction of oxidative stress. In a cell‐free assay, TF‐2A and TF‐2B reacted directly with reduced glutathione (GSH), in a time‐ and concentration‐dependent manner. Intracellular storages of GSH were depleted on treatment of the cells with the theaflavin monomers. Depletion of intracellular GSH was more extensive with TF‐2A than with TF‐2B and was more pronounced in the carcinoma, than in the normal, cells. The toxicities of the theaflavins were potentiated when the cells were cotreated with the GSH depleter, d,l‐buthionine‐[S,R]‐sulfoximine. In the presence of catalase, pyruvate and divalent cobalt, all scavengers of reactive oxygen species, the cytotoxicities of the theaflavins were lessened. TF‐2A and TF‐2B induced lipid peroxidation in the carcinoma cells, whereas in the fibroblasts, peroxidation was evident upon exposure to TF‐2A, but not to TF‐2B. These studies demonstrated that the black tea theaflavin monomers, TF‐2A and TF‐2B, act as prooxidants and induce oxidative stress, with carcinoma cells more sensitive than normal fibroblasts.
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.
A Method for Computing the Three-Dimensional Angular Velocity and Acceleration of a Body Segment From Three-Dimensional Position Data
Authors: Verstraete M. C. , Soutas-Little R. W.
Published: March 2008

A theoretical technique, based on the Method of Least Squares, was employed to solve for the three-dimensional components of the angular velocity and acceleration of a limb segment directly from experimentally recorded three-dimensional position data. Results showed that a minimum of four targets placed on the body segment, forming six relative position vector equations, were required to produce the most accurate results. It was also found that this method eliminates the errors due to soft tissue motion and system noise.
A Dynamic Finite Element Analysis of Impulsive Loading of the Extension-Splinted Rabbit Knee
Authors: Anderson D. D. , Brown T. D. , Yang K. H. , Radin E. L.
Published: March 2008

A dynamic nonlinear finite element model was developed to study juxtarticular stresses in the splinted rabbit knee, an established laboratory model for creating osteoarthrosis due to impulsive loading. Plane strain finite element results were validated by comparison with corresponding experimental data. Parametric effects studied included the input tibial displacement speed, the local bone density distribution, and the modulus of cartilage and subchondral bone. While the computed resultant contact force magnitude was sensitive to a number of model parameters, the stress patterns, when normalized to a given resultant force magnitude, were not. Despite comparable force peaks, the finite element results showed approximately six-fold higher effective strain rate levels for a severely impulsive loading protocol known to induce rapid osteoarthrosis, versus those for a mildly impulsive loading protocol not usually associated with cartilage damage. A propensity for elevated shear in the deep cartilage layer near the contact periphery, observed in nearly all computed stress distributions, is consistent with previous experimental findings of fissuring at that level in the impulsively loaded rabbit knee.
The Effect of Damage to the Lateral Collateral Ligaments on the Mechanical Characteristics of the Ankle Joint—An In-Vitro Study
Authors: Siegler S. , Chen Jie , Schneck C. D.
Published: March 2008

Injuries to the lateral collateral ligaments of the ankle joint are among the most frequently occurring injuries at the lower limb. The present study was conducted for the purpose of establishing the basis for the development of a quantitative diagnostic procedure for such injuries. To achieve this goal, the effect of four types of ligament injuries on the three-dimensional mechanical characteristics of the ankle were investigated. These types of injuries consisted of: 1) isolated tear of the anterior talofibular ligament; 2) isolated tear of the calcaneofibular ligament; 3) isolated tear of the posterior talofibular ligament; and 4) combined tear of both the anterior talofibular ligament and the calcaneofibular ligament. The experiments were conducted on 31 amputated lower limbs and consisted of comparing the three-dimensional load-displacement and flexibility characteristics of the ankle joint prior to and following sectioning of selected ligaments. The experimental and analytical procedures used to derive these characteristics was developed previously by the authors [3, 24]. From the results of this study it was concluded that the three-dimensional flexibility characteristics of the ankle joint are strongly influenced by damage to the lateral collateral ligaments. Furthermore, it was found that each type of ligament injury produced unique and identifiably changes in the flexibility characteristics of the ankle. These unique changes, which are described in detail in this paper, can be used to discriminate between the different types of ligament injuries. Consequently, it was concluded that it is feasible to develop a quantitative diagnostic procedure for ankle ligament injuries based on the effect of the injury on the flexibility characteristics of the ankle.
Effects of Friction on the Unconfined Compressive Response of Articular Cartilage: A Finite Element Analysis
Authors: Spilker Robert L. , Suh Jun-Kyo , Mow Van C.
Published: March 2008

A finite element analysis is used to study a previously unresolved issue of the effects of platen-specimen friction on the response of the unconfined compression test; effects of platen permeability are also determined. The finite element formulation is based on the linear KLM biphasic model for articular cartilage and other hydrated soft tissues. A Galerkin weighted residual method is applied to both the solid phase and the fluid phase, and the continuity equation for the intrinsically incompressible binary mixture is introduced via a penalty method. The solid phase displacements and fluid phase velocities are interpolated for each element in terms of unknown nodal values, producing a system of first order differential equations which are solved using a standard numerical finite difference technique. An axisymmetric element of quadrilateral cross-section is developed and applied to the mechanical test problem of a cylindrical specimen of soft tissue in unconfined compression. These studies show that interfacial friction plays a major role in the unconfined compression response of articular cartilage specimens with small thickness to diameter ratios.
The Effects of Temperature on the Viscoelastic Properties of the Rabbit Medial Collateral Ligament
Authors: Lam T. C. , Thomas C. G. , Shrive N. G. , Frank C. B. , Sabiston C. P.
Published: March 2008

There are disparate views on the effects of temperature on the mechanical properties of ligaments and tendons. We attempted to resolve the inconsistencies by testing the medial collateral ligaments of twelve, three-month old New Zealand white rabbits in both elastic-dominated and viscous-dominated tests between 25°C and 55°C. We found that in elastic-dominated monotonic loading, the loading portions of the loadextension curves were mathematically similar. Differences could be accounted for through a base-line shift of the origin caused by additional relaxation and thermal contraction/expansion of the apparatus and specimen. In tests where the viscous component of behavior was manifest, we found results similar to those of other investigators. Thus we conclude that in assessing the effects of temperature on the mechanical properties of tissues it is important to account for both temperature and initial positions of the apparatus and specimen, and to consider the effects of both relaxation and thermal contraction/expansion.
An Analysis of Pollutant Gas Transport and Absorption in Pulmonary Airways
Authors: Grotberg J. B. , Sheth B. V. , Mockros L. F.
Published: March 2008

A mathematical model of ozone absorption, or for any soluble gas that has similar transport properties, is developed for a branching network of liquid-lined cylinders. In particular, we investigate specific flow regimes for finite length tubes where boundary layer phenomena and entrance effects exist in high Reynolds and Peclet (Pe) number airways. The smaller airways which have lower Reynolds and Peclet number flows are modelled by incorporating the detailed analysis found in [10] and modifying it for airways which have alveolated surfaces. We also consider a reacting gas and treat specific regimes where the reaction front is located at the air-liquid interface, within the liquid or at the liquid-tissue interface. Asymptotic methods are used in regions of the tracheobronchial tree where Pe ≪1 and Pe≫ 1. In addition, the fact that the radial transport parameter Γ ≪1 for this toxin, and others such as nitrous oxides, is employed to simplify the analysis. The ozone concentrations, airway absorption and tissue dose are examined as a function of airway generation for several values of the governing parameters. The general result is a maximal dosing in airway generations 17 to 18 that is much larger (up to an order of magnitude) than the predictions of previous theories.
The Effect of Compliance on Wall Shear in Casts of a Human Aortic Bifurcation
Authors: Duncan D. D. , Bargeron C. B. , Borchardt S. E. , Deters O. J. , Gearhart S. A. , Mark F. F. , Friedman M. H.
Published: March 2008

Rigid and compliant casts of a human aortic bifurcation were subjected to physiologically realistic pulsatile fluid flows. At a number of sites near the wall in the approximate median plane of the bifurcation of these models, fluid velocity was measured with a laser Doppler velocimeter, and wall motion (in the case of the compliant cast) was determined with a Reticon linescan camera. The velocity and wall motion data were combined to estimate the instantaneous shear rates at the cast wall. Analysis showed that at the outer walls the cast compliance reduced shear rates, while at the walls of the flow divider the shear rate was increased.
Three-Dimensional Steady Flow Through A Bifurcation
Authors: Yung Chain-Nan , De Witt Kenneth J. , Keith Theo G.
Published: March 2008

Steady flow of an incompressible, Newtonian fluid through a symmetric bifurcated rigid channel was numerically analyzed by solving the three-dimensional Navier-Stokes equations. The upstream Reynolds number ranged from 100 to 1500. The bifurcation was symmetrical with a branch angle of 60 deg and the area ratio of the daughter to the mother vessel was 2.0. The numerical procedure utilized a coordinate transformation and a control volume approach to discretize the equations to finite difference form and incorporated the SIMPLE algorithm in performing the calculation. The predicted velocity pattern was in qualitative agreement with experimental measurements available in the literature. The results also showed the effect of secondary flow which can not be predicted using previous two-dimensional simulations. A region of reversed flow was observed near the outer wall of the branch except for the case of the lowest Reynolds number. Particle trajectory was examined and it was found that no fluid particles remained within the recirculation zone. The shear stress was calculated on both the inner and the outer wall of the branch. The largest wall shear stress, located in the vicinity of the apex of the branch, was of the same order of magnitude as the level that can cause damage to the vessel wall as reported in a recent study.
On the Application of a Constitutive Equation for Whole Human Blood
Authors: Rodkiewicz C. M. , Sinha Prawal , Kennedy J. S.
Published: March 2008

In consideration of the pulsatile blood flow in a conduit, the consitutive equation for the whole human blood of F. J. Walburn and D. J. Schneck (Biorheology, Vol. 13, 1976, pp. 201-210) is utilized. Governing equations are solved numerically yielding the velocity and the shear stress distributions. These results are discussed and compared with the Newtonian fluid, Casson’s fluid, and Bingham fluid applications.
Theoretical Analysis of the Effect of Convective Flow on Solute Transport and Insulin Release in a Hollow Fiber Bioartificial Pancreas
Authors: Pillarella M. R. , Zydney A. L.
Published: March 2008

The bioartificial pancreas, in which transplanted pancreatic tissue or isolated cells are cultured on a hollow fiber membrane, is an attractive approach to restore physiologic insulin delivery in the treatment of diabetes. Insulin response in prototype devices has been unacceptable due to the large mass transport limitations associated with the membrane and the surrounding shell region. Although available theoretical analyses provide some insight into the combined effects of transport and reaction in the bioartificial pancreas, they cannot quantitatively account for the effects of convective recirculation flow, complex intrinsic insulin secretory kinetics, and nonuniform distribution of pancreatic cells. We have developed a detailed model for glucose and insulin transport and insulin secretion in the hollow fiber bioartificial pancreas based on the solution of the mass and momentum conservation equations describing flow and transport in the lumen, matrix, and shell. Model predictions are in good agreement with literature data obtained in a hollow fiber device with minimal radial convective flow. Although no quantitative data are available for a device with significant radial convection, model simulations demonstrate that convective recirculation flow can dramatically improve insulin response, allowing the device to accurately capture the bi-phasic insulin secretion characteristic of the normal physiologic response. Results provide fundamental insights into the coupling between kinetics and transport in the hollow fiber system and a rational basis for the design of clinical devices.
A Mathematical Method for the Measurement of Bone Motion With Skin-Mounted Accelerometers
Authors: Trujillo D. M. , Busby H. R.
Published: March 2008

The methods of dynamic programming and generalized crossvalidation are used to estimate the acceleration of bone motion using skin-mounted accelerometers. Numerical experiments are performed to demonstrate the usefulness and limitations of the methods.
Bilayer Membrane Bending Stiffness by Tether Formation From Mixed PC-PS Lipid Vesicles
Authors: Song J. , Waugh R. E.
Published: March 2008

Recently, a new approach to measure the bending stiffness (curvature elastic modulus) of lipid bilayer membrane was developed (Biophys. J., Vol. 55; pp. 509–517, 1989). The method involves the formation of cylindrical membrane strands (tethers) from bilayer vesicles. The bending stiffness (B) can be calculated from measurements of the tether radius (Rt) as a function of the axial force (f) on the tether: B =f·Rt/2π. In the present report, we apply this method to determine the bending stiffness of bilayer membranes composed of mixtures of SOPC (1-stearoyl-2-oleoyl phosphatidyl choline) and POPS (1-palmitoyl-2-oleoyl phosphatidyl serine). Three different mixtures were tested: pure SOPC, SOPC plus 2 percent (mol/mol) POPS, and SOPC plus 16 percent POPS. The bending stiffness determined for these three different lipid mixtures were not significantly different (1.6–1.8×10-12 ergs). Because POPS carries a net negative charge, these results indicate that changes in the density of the membrane surface charge have no effect on the intrinsic rigidity of the membrane. The values we obtain are consistent with published values for the bending stiffness of other membranes determined by different methods. Measurements of the aspiration pressure, the tether radius and the tether force were used to verify a theoretical relationship among these quantities at equilibrium. The ratio of the theoretical force to the measured force was 1.12 ± 0.17.