bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of the Effects of Amitriptyline and Flunarizine on Weight Gain and Serum Leptin, C Peptide and Insulin Levels when used as Migraine Preventive Treatment
Authors: Berilgen MS , Bulut S , Gonen M , Tekatas A , Dag E , Mungen B
Published: October 2005

The tricyclic antidepressant amitriptyline (AMT) and the calcium channel blocker flunarizine are frequently used in the preventive treatment of migraine, but the side-effect of prominent weight gain that frequently emerges during preventive treatment of migraine with these agents often leads to the discontinuation of therapy. In this study, we aimed to investigate the possible relationship between the weight gain associated with the use of these agents and serum levels of leptin, C-peptide and insulin in patient with migraine. Forty-nine migraine patients with a body mass index (BMI) < 25 and without any endocrinological, immunological or chronic diseases were randomly divided into two groups, receiving AMT or flunarizine. There was a statistically significant increase in serum levels of leptin, C-peptide, insulin and measures of BMI in both groups when measured at the 12th week of therapy compared to their respective basal levels. To our knowledge this is the first study investigating the effects of AMT and flunarizine on serum leptin levels in preventive use of migraine treatment. A result from this study indicates that AMT and flunarizine may cause leptin resistance possibly by different mechanisms and thereby result in increase in serum leptin levels and BMI.
Experimental Induction of Muscle Tenderness and Headache in Tension-Type Headache Patients
Authors: Christensen MB , Bendtsen L , Ashina M , Jensen R
Published: October 2005

The aim of the present study was to investigate the impact of static contraction of the shoulder and neck muscles on muscle tenderness and headache in patients with tension-type headache. Twenty patients with frequent episodic tension-type headache and 20 healthy age- and sex-matched controls were examined using a placebo-controlled cross-over design. The subjects performed static contraction of the trapezius muscles (active procedure) or the anterior tibial muscles (placebo procedure) with 10% of maximal force for 30 min. Total tenderness score, local tenderness score and headache intensity were evaluated before and after the static work. Changes in headache intensity were followed for 24 h. Pericranial tenderness increased significantly more in patients than in controls after the active procedure ( P = 0.04). The increase in pericranial tenderness tended to be higher after the active procedure than after the placebo procedure in patients ( P = 0.08) and in controls ( P = 0.07). Sixty per cent of the patients and 20% of the healthy controls developed headache after the active procedure. Fifty per cent of the patients and none of the controls developed headache after the placebo procedure. There was no significant difference in headache development between the active and the placebo procedure in patients or controls. These findings demonstrate that tension-type headache patients are more liable to develop shoulder and neck pain in response to static exercise than healthy controls.
The Postdrome of the Acute Migraine Attack
Authors: Kelman L
Published: October 2005

This study was performed to document the frequency, duration and types of symptoms of postdrome in migraine patients. Eight hundred and twenty-seven consecutive headache clinic patients (IHS 1.1, 1.2 and 1.5.1) were evaluated at first visit. Postdrome frequency, duration and characteristics were analysed. Sixty-eight per cent of 827 patients reported postdrome (69.1% females; 56.8% males, P < 0.007). The average duration of the postdrome was 25.2 h. Fifty-six per cent had postdrome for ≤ 12 h, 32% for 12–24 h, 88% for ≤ 24 h, and 12% for > 24 h. The commonest symptoms were tiredness (71.8%), head pain (33.1%), cognitive difficulties (11.7%), ‘hangover’ (10.7%), gastrointestinal symptoms (8.4%), mood change (6.8%), and weakness (6.2%). Patients with postdrome compared with patients without postdrome have more characteristic and more frequent migraine features. This study demonstrated postdrome in 68% of patients, duration ≤ 24 h in most patients, more often associated with a full-blown migraine attack, more common in females, and with commonest symptoms being tiredness and low-grade headache.
Primary Headaches Associated with Sexual Activity—some Observations in Indian Patients
Authors: Chakravarty A
Published: October 2005

Primary headache associated with sexual activity appears to be relatively uncommon in a clinic-based study in Indian patients. Only 24 patients (M : F 18 : 6) were encountered over a 20-year period (1985–2004). Of the 18 male patients, 14 (age 33–42 years) had preorgasmic headache of tension-headache type for 2–8 months, one patient (age 58 years) had orgasmic headache of vascular type for 1 month and three subjects (age 19–23 years) had masturbatory headache also simulating tension-type headache for 3–7 weeks. These observations are at variance with those generally reported from western countries. Of the six female patients, four (age 26–32 years) had typical orgasmic headache of the vascular type (for a few months to a few years), only one of whom had been a migraine sufferer. One patient (age 35 years) presented with a single episode of thunderclap headache where angiography had been negative. Another female subject (age 30 years) experienced typical orgasmic headache only during masturbation but not during actual sexual intercourse. Occurrence of sexual headaches in both male and female subjects had been unpredictable. Few had associated migraine and none ever experienced exertional headache.
Biochemical Changes in Endocannabinoid System are Expressed in Platelets of Female but not Male Migraineurs
Authors: Cupini LM , Bari M , Battista N , Argirò G , Finazzi-Agrò A , Calabresi P , Maccarrone M
Published: October 2005

The endogenous cannabinoid anandamide (AEA) plays important roles in modulating pain. Head pain is an almost universal human experience, yet primary headache disorders, such as migraine without aura (MoA) or episodic tension-type headache (ETTH), can represent a serious threat to well-being when frequent and disabling. We assessed the discriminating role of endocannabinoids among patients with ETTH or MoA, and control subjects. We measured the activity of AEA hydrolase and AEA transporter, and the level of cannabinoid receptors in peripheral platelets from MoA, ETTH and healthy controls. Sixty-nine headache patients and 36 controls were selected. Diagnosis of headache type was made according to the International Headache Society criteria. We observed significant sex differences concerning AEA membrane transporter and fatty acid amide hydrolase activity in all groups. An increase in the activity of AEA hydrolase and AEA transporter was found in female but not male migraineurs. Cannabinoid receptors were the same in all groups. Here we show that the endocannabinoid system in human platelets is altered in female but not male migraneurs. Our results suggest that in migraineur women an increased AEA degradation by platelets, and hence a reduced concentration of AEA in blood, might reduce the pain threshold and possibly explain the prevalence of migraine in women. The involvement of the endocannabinoid system in migraine is new and broadens our knowledge of this widespread and multifactorial disease.
Forward Head Posture and Neck Mobility in Chronic Tension-Type Headache
Authors: Fernández-de-las-Peñas C , Alonso-Blanco C , Cuadrado ML , Pareja JA
Published: October 2005

Forward head posture (FHP) and neck mobility were objectively assessed in 25 patients with chronic tension-type headache (CTTH) and 25 healthy controls. Side-view pictures were taken in a sitting position to measure the craniovertebral angle. A cervical goniometer was employed to measure the range of all cervical motions. Patients with CTTH showed a smaller cranio-vertebral angle (45.3° ± 7.6°) than controls (54.1° ± 6.3°), thus presenting a greater FHP ( P < 0.001). Patients also had lesser neck mobility for all cervical movements, except for right lateral flexion ( P < 0.01). There was a positive correlation between the craniovertebral angle and neck mobility. Within the CTTH group, a negative correlation was found between the cranio-vertebral angle and headache frequency, but neck mobility did not correlate with headache parameters. Further research is needed to define a potential role of FHP and restricted neck mobility in the origin or maintenance of TTH.
Changes in gustatory function during the course of pregnancy and postpartum
Authors: Ochsenbein‐Kölble Nicole , Von Mering Ruth , Zimmermann Roland , Hummel Thomas
Published: October 2005

Objective  To investigate changes in gustatory function during pregnancy and postpartum.

Design  Prospective study.

Setting  Obstetric outpatient clinic, Zurich University Hospital.

Population  Forty‐four pregnant women, 46 controls.

Methods  A threshold‐like measure of gustatory function was obtained for different concentrations of the four basic tastes using ‘taste tablets’; subjects were also asked to rate the intensity and pleasantness/unpleasantness of suprathreshold taste solutions. Tests were performed in early pregnancy up to 14 weeks of gestational age, 8–12 weeks after the first and second examination and at least 6 weeks after birth. In parallel, controls were tested four times at intervals of 8–12 weeks.

Main outcome measures  Gustatory score (number of correctly identified tastes).

Results  Pregnant subjects exhibited a decreased gustatory function compared with non‐pregnant controls, still being present after birth. These ‘objective’ changes were observed although pregnant women rated the intensity of suprathreshold taste stimuli not significantly different from controls. Pregnant women rated salty stimuli to be more pleasant during the second trimester while they rated the salty stimuli to be less pleasant during the first and third trimester, and after birth.

Conclusions  Pregnancy is accompanied by changes in gustatory function. Decreased gustatory sensitivity may allow pregnant and breastfeeding women to vary their diet in order to consume adequate electrolytes. The discrepancy between ‘objective’ and ‘subjective’ findings in gustatory function may relate to changes in central processing of gustatory information during pregnancy.
The Consistency of Extinction Risk Classification Protocols
Authors: REGAN TRACEY J. , BURGMAN MARK A. , McCARTHY MICHAEL A. , MASTER LAWRENCE L. , KEITH DAVID A. , MACE GEORGINA M. , ANDELMAN SANDY J.
Published: October 2005

Abstract:  Systematic protocols that use decision rules or scores are seen to improve consistency and transparency in classifying the conservation status of species. When applying these protocols, assessors are typically required to decide on estimates for attributes that are inherently uncertain. Input data and resulting classifications are usually treated as though they are exact and hence without operator error. We investigated the impact of data interpretation on the consistency of protocols of extinction risk classifications and diagnosed causes of discrepancies when they occurred. We tested three widely used systematic classification protocols employed by the World Conservation Union, NatureServe, and the Florida Fish and Wildlife Conservation Commission. We provided 18 assessors with identical information for 13 different species to infer estimates for each of the required parameters for the three protocols. The threat classification of several of the species varied from low risk to high risk, depending on who did the assessment. This occurred across the three protocols investigated. Assessors tended to agree on their placement of species in the highest (50–70%) and lowest risk categories (20–40%), but there was poor agreement on which species should be placed in the intermediate categories. Furthermore, the correspondence between the three classification methods was unpredictable, with large variation among assessors. These results highlight the importance of peer review and consensus among multiple assessors in species classifications and the need to be cautious with assessments carried out by a single assessor. Greater consistency among assessors requires wide use of training manuals and formal methods for estimating parameters that allow uncertainties to be represented, carried through chains of calculations, and reported transparently.
Research Training for Releasable Animals
Authors: BAUER GORDON B.
Published: October 2005

Abstract:  Restrictions on training potentially releasable animals such as those undergoing rehabilitation care or wild‐caught captives have limited our understanding of sensory processes, cognition, and physiology important for conservation of species. It is common practice among several U.S. federal agencies to limit training of animals available for release. The behavioral argument justifying this practice is that training habituates subjects to people and conditions them to associate people with rewards such as food; habituation to and positive associations with people will lead animals into dangerous situations after their release. If under special circumstances research training is permitted, all trained behaviors must be extinguished before release because behaviors will transfer to the natural setting. Research on animal learning and memory indicates that these may not be accurate scenarios. A review of the literature on habituation, classical and instrumental conditioning, and compound conditioning suggests that learning within a research setting does not add to learning that already occurs in procedures associated with basic feeding and care. In fact, animals probably learn less about people in a training setting. Furthermore, context‐specific effects on memory limit behavior transfer from captive to natural settings. Extinction is strongly susceptible to context effects, which suggests that extinction does not effectively transfer to the postrelease setting. Counterintuitively, extinction of responses to experimental stimuli under some circumstances may enhance undesirable learning about humans. Under those circumstances in which isolation from human contact is difficult or undesirable, behavioral research can present an ideal format for minimizing learning about humans and provide biological information important for conservation.
A Landscape Approach to Biodiversity Conservation of Sacred Groves in the Western Ghats of India
Authors: BHAGWAT SHONIL A. , KUSHALAPPA CHEPPUDIRA G. , WILLIAMS PAUL H. , BROWN NICK D.
Published: October 2005

Abstract: Although sacred groves are important for conservation in India, the landscape that surrounds them has a vital influence on biodiversity within them. Research has focused on tree diversity inside these forest patches. In a coffee‐growing region of the Western Ghats, however, landscape outside sacred groves is also tree covered because planters have retained native trees to provide shade for coffee plants. We examined the diversity of trees, birds, and macrofungi at 58 sites—10 forest‐reserve sites, 25 sacred groves, and 23 coffee plantations— in Kodagu district. We measured landscape composition and configuration around each site with a geographic information system. To identify factors associated with diversity we constructed multivariate models by using a decision‐tree technique. The conventional measures of landscape fragmentation such as patch size did not influence species richness. Distance of sacred groves from the forest reserve had a weak influence. The measures of landscape structure (e.g., tree cover in the surroundings) and stand structure (e.g., variability in canopy height) contributed to the variation in species richness explained by multivariate models. We suggest that biodiversity present within sacred groves has been influenced by native tree cover in the surrounding landscape. To conserve this biodiversity the integrity of the tree‐covered landscape matrix will need to be conserved.
A Case Study in Applying the IUCN Regional Guidelines for National Red Lists and Justifications for their Modification
Authors: KELLER VERENA , ZBINDEN NIKLAUS , SCHMID HANS , VOLET BERNARD
Published: October 2005

Abstract: The World Conservation Union (IUCN) published guidelines to apply the criteria developed for global red lists at subglobal levels. So far only a few national red lists have been prepared according to these regional guidelines. We present a procedure based on the regional guidelines that was developed for the most recent red list of breeding birds in Switzerland. Special attention was given to step 2 of the IUCN regional guidelines, which consists of adapting categories according to an assessment of the extent to which extinction risk of the national population is affected by populations in neighboring countries. To avoid subjective assessments we formalized this “up‐ and downgrading” procedure by defining rules to answer the questions asked in the regional guidelines. Some modifications to the assessment procedure were introduced to account for the specific situation of applying it to birds as a very mobile group and Switzerland as a small country. The up‐ and downgrading procedure resulted in a change in category for 49 of the 195 bird species assessed. Overall, 9 species were upgraded, 21 species were downgraded by one category, and 19 species were downgraded by two categories. Formalizing step 2 allowed consistent application of the regional guidelines for all species and will make future revisions of the national red list and comparisons between different lists easier.
Habituation of Adult Magellanic Penguins to Human Visitation as Expressed through Behavior and Corticosterone Secretion
Authors: WALKER BRIAN G. , DEE BOERSMA P. , WINGFIELD JOHN C.
Published: October 2005

Abstract:  Ecotourism is increasing worldwide; hence, it is important to know how wildlife are affected behaviorally and physiologically by human visitation. We studied the effects of human visitation on the Magellanic Penguins (Spheniscus magellanicus) at Punta Tombo, Argentina, by monitoring changes in defensive head turns and plasma corticosterone (a hormone secreted in response to stress) for penguins with and without a history of tourist visitation. Habituation to human visitation was rapid. In penguins with no previous exposure to tourists, the number of defensive head turns and level of plasma corticosterone decreased significantly within 5 days of one 15‐minute visit/day. Penguins living in tourist‐visited and undisturbed areas secreted more corticosterone when captured and restrained than penguins visited by a person. Penguins in tourist areas, however, did not show as strong a corticosterone response to capture and restraint as did penguins in areas without tourists. This difference was due to a decreased capability of the adrenocortical tissue to secrete corticosterone in tourist‐visited birds. Although our data show no direct negative effects of tourism on Magellanic Penguins at Punta Tombo, consequences of a modification of physiological capabilities (e.g., adrenocortical function) may not become apparent until much later in life. The physiological differences between tourist‐visited and undisturbed groups of Magellanic Penguins emphasize the importance of monitoring the effects of anthropogenic disturbances on wildlife at multiple levels.
A Natural Experiment on the Impact of Overabundant Deer on Forest Invertebrates
Authors: ALLOMBERT SYLVAIN , STOCKTON STEVE , MARTIN JEAN‐LOUIS
Published: October 2005

Abstract:  In large parts of North America and Europe, deer overabundance threatens forest plant diversity. Few researchers have examined its effects on invertebrate assemblages. In a natural experiment on Haida Gwaii (British Columbia, Canada), where Sitka black‐tailed deer (Odocoileus hemionus sitkensis) were introduced, we compared islands with no deer, with deer for fewer than 20 years, and with deer for more than 50 years. We sampled invertebrates in three habitat categories: forest edge vegetation below the browse line, forest interior vegetation below the browse line, and forest interior litter. In forest edge vegetation, invertebrate abundance and species density decreased with increasing length of browsing history. In forest interior vegetation, decrease was significant only on islands with more than 50 years of browsing. Insect abundance in the vegetation decreased eightfold and species density sixfold on islands browsed for more than 50 years compared with islands without deer. Primary consumers were most affected. Invertebrates from the litter showed little or no variation related to browsing history. We attributed the difference between vegetation‐dwelling and litter‐dwelling invertebrates to differences in the effect of browsing on their habitat. In the layer below the browse line deer progressively removed the habitat. The extent of litter habitat was not affected, but its quality changed. We recommend more attention be given to the effect of overabundant ungulates on forest invertebrate conservation with a focus on edge and understory vegetation in addition to litter habitat.
Designatable Units for Status Assessment of Endangered Species
Authors: GREEN DAVID M.
Published: October 2005

Abstract: Species status assessment and the conservation of biological diversity may require defining units below the species level to portray probabilities of extinction accurately and to help set priorities for conservation efforts. What those units should be has been debated in the scientific literature largely in terms of evolutionarily significant units (ESUs), but this discourse has had little impact on government policy with regard to status assessment. As with species concepts, the variously proposed ESU concepts have not been resolvable into a single approach. The need for a practicable procedure to identify infraspecific entities for status assignment is the motivation behind employing designatable units (DUs). In aid of a policy to prevent elements of biodiversity from becoming extinct or extirpated, DUs are determined during the process of resolving a species' conservation status according to broadly applicable guidelines. The procedure asks whether putative DUs are distinguishable based on a reliably established taxonomy or a well‐corroborated phylogeny, compelling evidence of genetic distinction, range disjunction, and/or biogeographic distinction as long as extinction probabilities also differ. The language of the DU approach avoids wording that implies value judgments concerning evolutionary importance or significance. Because species conservation status assessment is not science but, rather, the use of science to further policy, DUs contribute to a precautionary approach to listing whereby status may be assessed even though knowledge of systematic relationships below the species level may be lacking or unresolved. The pragmatic approach of using DUs has been adopted by the Committee on the Status of Endangered Wildlife in Canada for status assessment of species under the Canadian Species at Risk Act.
Relative Fitness and Frailty of Elderly Men and Women in Developed Countries and Their Relationship with Mortality
Authors: Mitnitski Arnold , Song Xiaowei , Skoog Ingmar , Broe GA , Cox Jafna L. , Grunfeld Eva , Rockwood Kenneth
Published: October 2005

Objectives: To investigate the relationship between accumulated health‐related problems (deficits), which define a frailty index in older adults, and mortality in population‐based and clinical/institutional‐based samples.

Design: Cross‐sectional and cohort studies.

Setting: Seven population‐based and four clinical/institutional surveys in four developed countries.

Participants: Thirty‐six thousand four hundred twenty‐four people (58.5% women) aged 65 and older.

Measurements: A frailty index was constructed as a proportion of all potential deficits (symptoms, signs, laboratory abnormalities, disabilities) expressed in a given individual. Relative frailty is defined as a proportion of deficits greater than average for age. Measures of deficits differed across the countries but included common elements.

Results: In each country, community‐dwelling elderly people accumulated deficits at about 3% per year. By contrast, people from clinical/institutional samples showed no relationship between frailty and age. Relative fitness/frailty in both sexes was highly correlated (correlation coefficient >0.95, P<.001) with mortality, although women, at any given age, were frailer and had lower mortality. On average, each unit increase in deficits increased by 4% the hazard rate for mortality (95% confidence interval=0.02–0.06).

Conclusion: Relative fitness and frailty can be defined in relation to deficit accumulation. In population studies from developed countries, deficit accumulation is robustly associated with mortality and with age. In samples (e.g., clinical/institutional) in which most people are frail, there is no relationship with age, suggesting that there are maximal values of deficit accumulation beyond which survival is unlikely.
Physical and Mental Health Status of Older Long‐Term Cancer Survivors
Authors: Keating Nancy L. , Nørredam Marie , Landrum Mary Beth , Huskamp Haiden A. , Meara Ellen
Published: October 2005

Objectives: To assess the physical and mental health status of older long‐term cancer survivors.

Design: Cohort study using propensity score methods to control for baseline differences between cancer survivors and controls.

Setting: General community population in the United States.

Participants: Nine hundred sixty‐four cancer patients who had survived for more than 4 years and 14,333 control patients who had never had cancer from a population‐based sample of Americans aged 55 and older responding to the 2002 Health and Retirement Study.

Measurements: Medical conditions, symptoms, health behaviors, health status, mobility, activities of daily living, mental health diagnoses, self‐rated memory, depressive symptoms, cognitive function, and self‐reported life expectancy.

Results: Cancer survivors reported higher rates of lung disease (13.9% vs 9.6%; P=.001), heart condition (29.3% vs 22.9%; P<.001), arthritis (69.4% vs 59.4%; P<.001), incontinence (26.6% vs 19.7%; P=.001), frequent pain (36.4% vs 29.4%; P=.005), and obesity (27.0% vs 24.2%; P=.001) than individuals without cancer but lower rates of smoking (12.0% vs 14.8%; P=.03). Cancer survivors were less likely than persons without cancer to report excellent or very good health status (37.2% vs 44.6%; P<.001) and had more mobility (P<.001) and activity of daily living (P=.01) limitations. Cancer survivors did not differ from persons without cancer in rates of depression or cognitive function (both P>.2) but were less optimistic about their life expectancy (P=.004).

Conclusion: The physical health status of older long‐term cancer survivors is somewhat worse than that of comparable persons who have never had cancer, but they have surprisingly similar mental health status. Future research is needed to understand factors contributing to poorer health status and identify patients at highest risk of long‐term cancer‐related problems.
Expression of macrophage migration inhibitory factor in rat skin during embryonic development
Authors: Shimizu Tadamichi , Ogata Akihiko , Honda Ayumi , Nishihira Jun , Watanabe Hirokazu , Abe Riichiro , Zhao Yunan , Shimizu Hiroshi
Published: October 2005

Abstract:  We have previously shown that human epidermal keratinocytes express macrophage migration inhibitory factor (MIF) mRNA, and immunohistochemical studies showed that MIF is expressed in human epidermis. To explore the possible pathophysiological roles of MIF in skin during rat fetal development, we examined the expression patterns of MIF during rat epidermal development using Northern blot analysis and in situ hybridization. Expression of MIF mRNA was first detected by in situ hybridization in the developing epidermis and hair germ cells from embryonic day (ED) 16. From ED 19, moderate levels of MIF expression were detected in the epidermis and epithelial sheath cells of growing hair follicles. In postnatal rat skin, higher MIF expression was detected in the epidermis and hair follicles on postnatal day 3. These observations were also confirmed by Northern blot analysis. Immunohistochemical analysis with an anti‐MIF antibody showed a similar distribution to that of the mRNA. Our results suggest that MIF is associated with epidermal and hair follicle development.
Zinc as an ambivalent but potent modulator of murine hair growth in vivo– preliminary observations
Authors: Plonka Przemyslaw M. , Handjiski Bori , Popik Malgorzata , Michalczyk Dominika , Paus Ralf
Published: October 2005

Abstract:  Oral zinc (Zn2+) is often employed for treating hair loss, even in the absence of zinc deficiency, although its mechanisms of action and efficacy are still obscure. In the current study, we explored the in vivo effects of oral zinc using the C57BL/6 mouse model for hair research. Specifically, we investigated whether continuous administration of high‐dose ZnSO4 × 7H2O (20 mg/ml) in drinking water affects hair follicle (HF) cycling, whether it retards or inhibits chemotherapy‐induced alopecia (CIA) and whether it modulates the subsequent hair re‐growth pattern. Here, we show that high doses of oral zinc significantly inhibit hair growth by retardation of anagen development. However, oral zinc also significantly retards and prolongs spontaneous, apoptosis‐driven HF regression (catagen). Oral zinc can also retard, but not prevent, the onset of CIA in mice. Interestingly, Zn2+ treatment of cyclophosphamide‐damaged HFs also significantly accelerates the re‐growth of normally pigmented hair shafts, which reflects a promotion of HF recovery. However, if given for a more extended time period, zinc actually retards hair re‐growth. Thus, high‐dose oral zinc is a powerful, yet ambivalent hair growth modulator in mice, whose ultimate effects on the HF greatly depend on the timing and duration of zinc administration. The current study also encourages one to explore whether oral zinc can mitigate chemotherapy‐induced hair loss in humans and/or can stimulate hair re‐growth.
Kinesin‐2 is a Motor for Late Endosomes and Lysosomes
Authors: Brown Christa L. , Maier Kerstin C. , Stauber Tobias , Ginkel Laura M. , Wordeman Linda , Vernos Isabelle , Schroer Trina A.
Published: October 2005

The bidirectional nature of late endosome/lysosome movement suggests involvement of at least two distinct motors, one minus‐end directed and one plus‐end directed. Previous work has identified dynein as the minus‐end‐directed motor for late endosome/lysosome localization and dynamics. Conventional kinesin (kinesin‐1) has been implicated in plus‐end‐directed late endosome/lysosome movement, but other kinesin family members may also be involved. Kinesin‐2 is known to drive the movement of pigment granules, a type of lysosomally derived organelle, and was recently found to be associated with purified late endosomes. To determine whether kinesin‐2 might also power endosome movement in non‐pigmented cells, we overexpressed dominant negative forms of the KIF3A motor subunit and KAP3 accessory subunit and knocked down KAP3 levels using RNAi. We found kinesin‐2 to be required for the normal steady‐state localization of late endosomes/lysosomes but not early endosomes or recycling endosomes. Despite the abnormal subcellular distribution of late endosomes/lysosomes, the uptake and trafficking of molecules through the conventional endocytic pathway appeared to be unaffected. The slow time–course of inhibition suggests that both kinesin‐2 itself and its attachment to membranes do not turn over quickly.
Cytoplasmic Transport Signal is Involved in Phogrin Targeting and Localization to Secretory Granules
Authors: Torii Seiji , Saito Naoya , Kawano Ayumi , Zhao Shengli , Izumi Tetsuro , Takeuchi Toshiyuki
Published: October 2005

Phogrin is an integral glycoprotein primarily expressed in neuroendocrine cells. The predominant localization of phogrin is on dense‐core secretory granules, and the lumenal domain has been shown to be involved in its efficient sorting to the regulated secretory pathway. Here, we present data showing that a leucine‐based sorting signal [EExxxIL] within the cytoplasmic tail contributes its steady‐state localization to secretory granules. Deletion mutants in the tail region failed to represent granular distribution in pancreatic β‐cell line, MIN6, and anterior pituitary cell line, AtT‐20. A sorting signal mutant with two glutamic acids substituted into alanines (EE/AA) is primarily accumulated in the Golgi area instead of secretory granules, and another mutant (IL/AA) is trapped at the plasma membrane due to a defect in endocytosis. We further demonstrate that the leucine‐based sorting signal of phogrin specifically interacts with both adaptor protein (AP)‐1 and AP‐2 clathrin adaptor complexes in vitro. These observations, along with previous studies, suggest that distinct domains of phogrin mediate proper localization of this transmembrane protein on secretory granules.
Tissue engineering osteochondral implants for temporomandibular joint repair
Authors: Schek RM , Taboas JM , Hollister SJ , Krebsbach PH
Published: October 2005

Authors –  Schek RM, Taboas JM, Hollister SJ, Krebsbach PH  

Tissue engineering has provided an alternative to traditional strategies to repair and regenerate temporomandibular joints (TMJ). A successful strategy to engineer osteochondral tissue, such as that found in the TMJ, will produce tissue that is both biologically and mechanically functional. Image‐based design (IBD) and solid free‐form (SFF) fabrication can be used to generate scaffolds that are load bearing and match patient and defect site geometry. The objective of this study was to demonstrate how scaffold design, materials, and biological factors can be used in an integrated approach to regenerate a multi‐tissue interface. IBD and SFF were first used to create biomimetic scaffolds with appropriate bulk geometry and microarchitecture. Biphasic composite scaffolds were then manufactured with the same techniques and used to simultaneously generate bone and cartilage in discrete regions and provide for the development of a stable interface between cartilage and subchondral bone. Poly‐l‐lactic acid/hydroxyapatite composite scaffolds were differentially seeded with fibroblasts transduced with an adenovirus expressing bone morphogenetic protein‐7 in the ceramic phase and fully differentiated chondrocytes in the polymeric phase, and were subcutaneously implanted into mice. Following implantation in the ectopic site, the biphasic scaffolds promoted the simultaneous growth of bone, cartilage, and a mineralized interface tissue. Within the ceramic phase, the pockets of tissue generated included blood vessels, marrow stroma, and adipose tissue. This combination of IBD and SFF‐fabricated biphasic scaffolds with gene and cell therapy is a promising approach to regenerate osteochondral defects and, ultimately, the TMJ.
Collagen gel delivery of Tgf‐β3 non‐viral plasmid DNA in rat osteoblast and calvarial culture
Authors: Premaraj S , Mundy B , Parker‐Barnes J , Winnard PL , Moursi AM
Published: October 2005

Authors –  Premaraj S, Mundy B, Parker‐Barnes J, Winnard PL, Moursi AM  

Different forms of collagen as a carrier for naked plasmid DNA have shown potential as vehicles for therapeutic gene delivery and tissue engineering. The objective of this study was to determine the suitability of a dense collagen gel as a vehicle for sustained delivery of plasmid DNA in cell and organ culture. Plasmid DNA encoding Tgf‐β3 was combined with collagen gel. DNA released into the media was measured by Pico‐Green spectrophotometry. Results showed that DNA was released from the collagen gel at a gradual rate for up to 14 days. To evaluate collagen‐mediated transfection in tissue, calvariae were exposed to collagen containing plasmid encoding GFP or DsRed. Transfection was visualized by fluorescence localized to tissue adjacent to the vehicle. To evaluate protein production, fetal rat calvarial osteoblasts were cultured with a collagen/Tgf‐β3 plasmid mixture or in media containing plasmid alone. Media was collected at various time points to measure Tgf‐β3 protein production. ELISA assays showed that collagen‐transfected osteoblasts demonstrated an elevated Tgf‐β3 protein production for up to 14 days. Therefore, collagen delivery of viable plasmid DNA created a sustained transient transfection of calvarial osteoblasts resulting in prolonged and elevated growth factor production. Together, these results suggest that use of collagen gel as a vehicle may provide a strategy to achieve localized and controlled, non‐viral gene delivery in vivo.
Intracerebroventricular Effects of Histaminergic Agents on Morphine‐Induced Anxiolysis in the Elevated Plus‐Maze in Rats
Authors: Zarrindast Mohammad‐Reza , Rostami Parvin , Zarei Morteza , Roohbakhsh Ali
Published: October 2005

Abstract: Some reports indicate that morphine can induce anxiolytic effects both in animal and in man. It has also been reported that histaminergic system can interfere with some pharmacological effects of morphine. The effects of histaminergic agents on morphine‐induced anxiolysis in rats, using elevated plus‐maze were investigated in the present study. Intraperitoneal injection of morphine (3, 6 and 9 mg/kg) induced antianxiety effects. Intracerebroventricular administration of histamine at the doses of (5, 10 and 20 μg/rat) also increased anxiety‐related behaviours. Intracerebroventricular injection of pyrilamine, a H1 receptor antagonist (25, 50 and 100 μg/rat), increased anxiety whereas injection of ranitidine, a H2 receptor antagonist (5, 10 and 20 μg/rat) at the same site, decreased anxiety. Therefore, it seems that histamine induces anxiogenic response through activation of H2 receptors, while the response of H1 blocker may be due to release of histamine. We also evaluated the interactions between morphine and histaminergic agents. Our data show that histamine (10 μg/rat), pyrilamine (50 μg/rat) and ranitidine (5 μg/rat) did not alter the response induced by different doses of morphine (3, 6 and 9 mg/kg). Similarly, a single dose of morphine did not alter the response induced by different doses of histamine (5, 10 and 20 μg/rat), pyrilamine (25, 50 and 100 μg/rat) or ranitidine (5, 10 and 20 μg/rat). In conclusion, the histaminergic system plays an important role in the modulation of anxiety, although in our experiments, no interaction was found between the effects of histaminergic agents and morphine on anxiety‐related indices in the elevated plus‐maze. This may imply that morphine‐induced anxiolysis probably is independent of the histaminergic system.
Protective Effects of Different Antioxidants and Amrinone on Vancomycin‐Induced Nephrotoxicity
Authors: Celik Ilhami , Cihangiroglu Mustafa , Ilhan Nevin , Akpolat Nusret , Akbulut H. Handan
Published: October 2005

Abstract: We have studied the effects of three antioxidants and amrinone, an inotropic agent, against vancomycin‐induced nephrotoxicity in rats by investigating renal function and morphology. Thirty adult female Sprague Dawley rats (168–234 g) were divided into six groups. A saline‐treated group served as control. The other five groups were treated for 7 days with vancomycin alone or in combination with α‐lipoic acid, Ginkgo biloba extract 761, melatonin or amrinone. On day 8, all the rats were sacrificed by decapitation, kidney tissues were excised immediately and blood and kidney samples were collected. Blood urea and creatinine, kidney tissue malondialdehyde levels, and kidney superoxide dismutase and glutathione (GSH) peroxidase activities were measured. The kidneys were also examined for histological changes. Vancomycin administration led to increased urea, creatinine and malondialdehyde levels and decreased superoxide dismutase and GSH peroxidase activities. Co‐administration of α‐lipoic acid, Ginkgo biloba extract, melatonin or amrinone with vancomycin prevented the increases in the urea, creatinine and melondialdehyde levels and also resulted in higher superoxide dismutase and GSH peroxidase activities. The antioxidants and AMR improved the renal pathology compared to rats treated with vancomycin alone (P<0.05). These results indicate that the three antioxidants and amrinone have potential protective effects against vancomycin‐induced nephrotoxicity, which might in part be due to inhibition of free oxygen radical production. Amrinone was the most effective drug as judged on the basis of the pathological findings.
Influence ofCYP2C9, 2C19and2D6Genetic Polymorphisms on the Steady‐State Plasma Concentrations of the Enantiomers of Fluoxetine and Norfluoxetine
Authors: Scordo Maria G. , Spina Edoardo , Dahl Marja‐Liisa , Gatti Giuliana , Perucca Emilio
Published: October 2005

Abstract:The antidepressant fluoxetine is administered as racemic mixture of two enantiomers (S‐ andR‐fluoxetine). WhileS‐ andR‐fluoxetine are equipotent in blocking serotonin reuptake, the enantiomers of the demethylated metabolite, norfluoxetine, show marked differences in pharmacological activity,S‐norfluoxetine being about 20 times as potent asR‐ norfluoxetine as a serotonin reuptake inhibitor.In vitroandin vivodata suggest that the metabolism of fluoxetine to norfluoxetine is stereoselective and mediated, at least in part, by the polymorphic cytochrome P450 (CYP) isoenzymes CYP2D6, CYP2C9 and CYP2C19. In the present study, the influence ofCYP2D6,CYP2C9andCYP2C19polymorphisms on the steady‐state plasma concentrations of fluoxetine and norfluoxetine enantiomers was evaluated in 78 patients receiving chronic fluoxetine treatment (10–60 mg/day). The plasma concentrations of fluoxetine and norfluoxetine enantiomers were measured andCYP2D6,CYP2C9andCYP2C19genotypes were analyzed. No statistically significant relationship was identified betweenCYP2D6orCYP2C19genotypes and the dose normalised plasma concentrations of any of the enantiomers or the active moiety (i.e. the sum ofS‐fluoxetine,R‐fluoxetine andS‐norfluoxetine). However, the plasma concentration ofS‐norfluoxetine was very low in the onlyCYP2D6poor metaboliser. Furthermore, the median S‐norfluoxetine/S‐fluoxetine ratios were higher in homozygous than in heterozygous extensive metabolisers (P<0.05). Among homozygous extensive metabolizers forCYP2D6, patients homozygous forCYP2C9*1had lower dose‐normalizedR‐fluoxetine concentrations and lower active moiety levels compared with those carrying detrimentalCYP2C9alleles (P<0.05). These results suggest thatCYP2D6andCYP2C9polymorphisms contribute to the interindividual variability in fluoxetine pharmacokinetics at steady‐state.
Study of the Pioneer anomaly: A problem set
Authors: Turyshev Slava G. , Nieto Michael Martin , Anderson John D.
Published: October 2005

Analysis of the radio-metric tracking data from the Pioneer 10 and 11 spacecraft at distances between 20 and 70 astronomical units from the Sun has consistently indicated the presence of an anomalous, small, and constant Doppler frequency drift. The drift is a blueshift, uniformly changing at the rate of (5.99±0.01)×10−9Hz∕s. The signal also can be interpreted as a constant acceleration of each spacecraft of (8.74±1.33)×10−8cm∕s2 directed toward the Sun. This interpretation has become known as the Pioneer anomaly. We provide a problem set based on the detailed investigation of this anomaly, the nature of which remains unexplained.
Max Born and the quantum theory
Authors: Bernstein Jeremy
Published: October 2005

The role of Max Born in the creation of the quantum theory is discussed. Some explanations as to why he received his Nobel Prize so late are offered.
Why does water change the pitch of a singing wineglass the way it does?
Authors: Chen Yih-Yuh
Published: October 2005

When the rim of a fine wineglass is rubbed with a moist finger, a pure tone can be heard. The frequency of this tone is lowered if a liquid such as wine or water is added to the glass. Although it is tempting to ascribe this change to the extra effective mass contributed to the wineglass by the liquid, we argue that this explanation leads to several counterintuitive phenomena. We use a simplified model to compute the frequency shift as well as a variational approach for a more general derivation and demonstrate how a more appropriate physical interpretation accounts qualitatively for all the observed phenomena.
Model study of the Landau–Zener approximation
Authors: Geltman Sydney , Aragon Nathan D.
Published: October 2005

We reexamine the accuracy of the Landau–Zener approximation, whose analytic simplicity has made it often cited and applied over the past 70years in describing nonadiabatic transitions. We find that this approximation may be in substantial disagreement with exact numerical results for a model physical system and a wide range of coupling strengths and relative velocities. We conclude that the Landau–Zener approximation should be used with caution for quantitative estimates of nonadiabatic transition probabilities or cross sections.
Ray tracing over smooth elastic shells of arbitrary shape
Authors: Yang Yang , Norris Andrew N. , Couchman Luise S.
Published: October 2005

An efficient numerical scheme based on ray theory is developed for the analysis of elastic waves traveling over a fluid-loaded smooth elastic shell of arbitrary shape. The shell’s surface is first discretized into a number of small patches. The local geometry of each patch is then approximated in a parametric form using bi-cubic spline functions. A local curvilinear coordinate frame is defined on each patch. The ray trajectories and ray-tube areas are obtained by solving a set of ordinary differential equations, the ray and transport equations, within each patch. Several numerical tests of the accuracy and efficiency of the scheme were carried out on spherical and ellipsoidal elastic shells. The numerical results for the spherical shell agree well with analytical solutions. The ray trajectories and the ray-tube areas over an ellipsoidal shell with three distinct semiaxes clearly illustrate the inhomogeneous and anisotropic effects due to the variable curvature on the shell’s surface. It is also observed numerically that the magnitude of the ray-tube area along a ray is directly correlated with the stability of its trajectory.
Leaky Rayleigh wave scattering from elastic media with random microstructures
Authors: Zhang Yuan , Weaver Richard L.
Published: October 2005

Scattering of leaky Rayleigh waves from a flat fluid–solid interface is studied. The fluid half-space is taken to be ideal and homogeneous while the solid half-space has randomly inhomogeneous anisotropic elastic constants due to the microstructure of the material. For plane waves incident from the fluid onto the interface at the critical Rayleigh angle the singly scattered incoherent field is obtained by utilizing a first Born approximation. When the solid is a crystal aggregate and when the correlation function is of exponential form, the mean-square scattered signal level is found to be inversely proportional to the dimensionless frequency in the geometrical (high-frequency) limit but proportional to the third power of frequency in the Rayleigh (low-frequency) limit. Numerical results are given for water–aluminum (cubic polycrystals) interface scattering.
The surface impedance of grounds with exponential porosity profiles
Authors: Raspet Richard , Sabatier James M.
Published: October 2005

Previous impedance models for grounds whose porosities vary exponentially with depth have been based on the microstructural theory of sound propagation in rigid porous materials. These models were derived by incorporating the spatial dependence of the complex wave number on the porosity into the wave equation. The predicted impedances do not behave as expected and produce nonphysical results for porosities which decrease with depth. In this paper the change in porosity is incorporated into the equivalent complex medium Euler equation and continuity equation and a new wave equation is derived. The solution to this wave equation produces physical meaningful results for exponentially decreasing porosity (the case for most naturally occurring ground surfaces) and produces well-behaved results for exponentially increasing porosity.