bluuebunny/crossref_metadata_2025 huggingface dataset:
Contribution of the functional dyad of animal toxins acting on voltage‐gated Kv1‐type channels
Authors: Mouhat Stephanie , De Waard Michel , Sabatier Jean‐Marc
Published: December 2004

The ‘functional dyad’, a well‐defined pair of amino acid residues (basic and hydrophobic residues), is a key molecular determinant present in most animal toxins acting on voltage‐gated Kv1 channels. It is increasingly used as a working concept to explain how toxins are able to recognize and block their specific ion channel targets. However, other crucial toxin determinants are emerging and the actual role of this ‘functional dyad’ ought to be clarified, which is the object of the present mini‐review. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd.
Absorption and luminescence characteristics of optically thin conjugated polymer films
Authors: Yang L. , Wu P. , Yeh H. , Zeng L. , Zhang Q. , Liu X. , Gu P.
Published: December 2004

Poly[(2‐methoxy,5‐octoxy)1,4‐phenylenevinylene] (MO‐PPV) optically thin films have been prepared from their chloroform solutions of different concentrations. Then their UV–Vis absorption (Abs), photoluminescence (PL), and selective‐excitation photoluminescence (SEPL) spectra have been measured at room temperature. The position of S0 → S1 absorption peak shows red shift and broadened relative to that in MO‐PPV solution form due to solidation effect, while no relative shifts between the absorption spectra of these film samples are observed. A “long‐wavelength tail” appears in Abs spectra which should attribute to the disorder morphology of these thin films. A long‐wavelength emission component near 630 nm has been identified as S2 → S0 vibronic band through Gaussian decomposition method and confirmed by below‐gap PL and selective‐excitation PL experiments. This absorption tail and the second vibronic band cannot be observed in thick films. The PL efficiency of MEH‐PPV thin film and that of MO‐PPV thin film are also compared and explained by the side substituent effect, which can be proved both by theoretical simulation of interchain interactions and by comparing their morphology in film forms. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Optical characteristics of thin rf sputtered Ta2O5 layers
Authors: Babeva Tz. , Atanassova E. , Koprinarova J.
Published: December 2004

The optical properties of rf sputtered (30; 52 nm) Ta2O5 before and after O2 annealing at 1173 K have been investigated in the terms of storage capacitor applications for high density dynamic memories. Refractive index and thickness of the films are determined from transmittance and reflectance measurements at normal light incidence in the spectral range 400–800 nm. The film density explored by refractive index is improved with increasing film thickness as well as after annealing. The optical band gap is found to be 4.20 eV for 30 nm and 4.12 eV for 52 nm Ta2O5 regardless of the amorphous status of the layers‐amorphous (as‐deposited) or polycrystalline (annealed layers). (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Photo‐ and radioluminescence of Pr‐doped Lu3Al5O12 single crystal
Authors: Nikl M. , Ogino H. , Krasnikov A. , Beitlerova A. , Yoshikawa A. , Fukuda T.
Published: December 2004

Photo‐ and radioluminescence characteristics of the Pr3+‐doped Lu3Al5O12 single crystal are reported and compared with those of Pr‐doped Y3Al5O12. With respect to the Y3Al5O12 host, lower emission quenching and better temperature stability round 300 K is obtained for the Pr3+ 5d–4f emission peaking round 308 nm and about a factor 2 higher radioluminescence intensity is observed around this temperature. The photoluminescence decay time is of about 17 ns, while the scintillation decay is dominated by the component of about 25 ns. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Intangible benefits of CMM‐based software process improvement
Authors: Hyde Kevin , Wilson David
Published: December 2004

Many software organisations today are endeavouring to improve their software development processes to improve product quality, project team productivity and reduce development cycle times, thereby increasing their competitiveness and profitability.

The Sydney‐based development section of a telecommunications outsourced organisation selected the Software Engineering Institute's Capability Maturity Model (CMM) as their model‐based approach to software process improvement. CMM‐based software process improvement may deliver both tangible and intangible benefits to an organisation. Both types of benefits have been reported in the literature by organisations that have undertaken CMM‐based software process improvement. The objective of this study is to investigate whether the case study development organisation, having recently been assessed at Level 2 on the CMM, is realising any intangible benefits.

Survey‐based research was conducted in the development organisation during the early 2000s to find out from software professionals if they believed the intangible benefits were being realised. The survey results showed that the organisation had experienced improvements in the quality of work life, organisation communications, organisation learning and efficiencies, the ability to attract, retain and develop software professionals and the coherency of its organisation culture. Copyright © 2004 John Wiley & Sons, Ltd.
Managing coordination and cooperation in distributed software processes: the GENESIS environment
Authors: Aversano Lerina , De Lucia Andrea , Gaeta Matteo , Ritrovato Pierluigi , Stefanucci Silvio , Luisa Villani Maria
Published: December 2004

We present the GENESIS platform (GEneralised eNvironment for procEsS management in cooperatIve Software engineering), the outcome of a research project aiming at designing and developing a noninvasive and open‐source system to support software engineering processes in a highly distributed environment. The system supports the cooperation and coordination in software processes as its process modeling language enables the decomposition of complex processes into subprocesses that can be distributed and executed at different organizational sites. In GENESIS, workflow management technologies have been integrated with artifact management and communication services to meet the necessary requirements of managing the cooperation among distributed teams. Its strengths are a powerful activity management, covering all the main aspects of the life cycle of an activity; an efficient and flexible project monitoring, collecting productivity and quality metrics to show on‐demand snapshots of the whole process and of its parts at different levels of detail, and a careful consideration of the process evolution questions, allowing to adequately manage the most common exceptions happening during process execution in a simple and flexible way. Copyright © 2004 John Wiley & Sons, Ltd.
Analysis of supported zirconocenes by x‐ray emission and absorption techniques
Authors: Loureiro Silvia R. , Silveira Fernando , Pires Gilvan P. , Alves Maria do C. , Stedile Fernanda C. , dos Santos João Henrique Z. , Bichinho Kátia M. , Teranishi Toshiharu
Published: December 2004

Metal contents in supported zirconocene catalysts were comparatively determined by x‐ray fluorescence spectroscopy and Rutherford backscattering spectrometry. A series of supported zirconocenes was prepared by grafting sequentially Cp2ZrCl2 (Cp = cyclopentadienyl) and (nBuCp)2ZrCl2 on to silica. The addition order and molar ratio of the two catalysts were varied. The grafted metal content was shown to be coherent between the two techniques and was between 0.37 and 0.53 wt% Zr/SiO2. The steric effect played by the ligand influences the final zirconocene grafted content. No influence of the grafting order was observed. Nevertheless, catalyst systems in which (nBuCp)2ZrCl2 was either immobilized in the first place or at a higher molar ratio were shown to be more active in ethylene polymerization. Extended x‐ray absorption fine structure analysis in the Zr‐edge showed that systems bearing Cp2ZrCl2 and (nBuCp)2ZrCl2 in a 1:3 molar ratio afforded a more disoriented system. According to electron probe microanalysis, the metal distribution in the catalyst particle was more uniform than that resulting from the immobilization of solely (nBuCp)2ZrCl2 on silica. Copyright © 2004 John Wiley & Sons, Ltd.
Analysis and localization of metal‐ and metalloid‐containing proteins by synchrotron radiation x‐ray fluorescence spectrometry
Authors: Kühbacher M. , Weseloh G. , Thomzig A. , Bertelsmann H. , Falkenberg G. , Radtke M. , Riesemeier H. , Kyriakopoulos A. , Beekes M. , Behne D.
Published: December 2004

Synchrotron radiation x‐ray fluorescence (SRXRF) spectrometry has been applied for the determination of metals and metalloids in electrophoretically separated proteins and histological samples. The method was tested by the analysis of trace element‐containing proteins in rat testis homogenate and the determination of the spatial distribution of some metals in brain sections of scrapie‐infected hamsters. After sodium dodecyl sulfate—polyacrylamide gel electrophoresis (SDS‐PAGE) and transfer on to a blotting membrane, the distribution of selenium among the proteins of testis homogenate was determined. The comparison with the autoradiogram of 75Se‐labeled testicular proteins separated in the same way showed that of nine selenium‐containing proteins found by autoradiography, four could be detected by SRXRF. The distribution of several metals and metalloids in cryo‐sections of 10 µm thin brain sections of three Syrian hamsters intracerebrally infected with the scrapie strain ME7‐H and of three control animals was investigated at the HASYLAB beamline L by scanning with a synchrotron radiation beam focused by a polycapillary lens. The copper‐binding prion protein (PrP) in its pathological form PrPSc, determined by immunohistochemistry on cryo‐sections, was found to be diffusely dispersed in the scrapie‐infected brains, and the copper distribution differed from that in the control animals. The question whether, and to what extent, PrPSc and copper hot‐spots are related, remains to be investigated. The method was shown to be suitable for the determination of trace element distribution patterns in electrophoretically separated proteins and histological tissue preparations. Copyright © 2004 John Wiley & Sons, Ltd.
Determination of L‐shell intensity ratios for Yb, Hf and Ta by a parameter refinement method
Authors: Carreras A. , Trincavelli J. , Bonetto R. , Castellano G.
Published: December 2004

Transition rates for radiative decays to the L‐shell were obtained for Yb, Hf and Ta by means of a method of experimental and atomic parameter refinement in x‐ray fluorescence. An analytical function accounts for continuum and characteristic radiation detection artifacts are also included in the spectral description. The procedure of parameter refinement consists of minimizing quadratic differences between the experimental and predicted spectra through the optimization of the parameters involved in the analytical expression used. Spectra were acquired in an energy‐dispersive system with synchrotron monochromatic beams. The results obtained for the sought transition rates are in agreement with the scarce values found in the literature. Copyright © 2004 John Wiley & Sons, Ltd.
Determination of Mg and Ti in Ziegler–Natta catalysts by x‐ray fluorescence spectrometry
Authors: Bichinho Kátia M. , Pires Gilvan Pozzobon , dos Santos João Henrique Z. , Wolf Carlos Rodolfo
Published: December 2004

The metal content in Ziegler–Natta catalysts based on Ti and Mg derivatives could not be determined directly by x‐ray fluorescence (XRF) spectrometry owing to the instability of the catalyst. The samples were then calcined and the resultant Mg and Ti oxides were characterized by x‐ray diffraction (XRD). A series of synthetic standards were prepared with high‐purity MgO and TiO2, since there were no available certified standards for the catalysts. Samples and standards were compressed with high‐purity H3BO3 flux. This protocol was shown to be reproducible, having a correlation coefficient of 0.9999. The metal contents determined by XRF were in accordance with those obtained by a complexometric titration (Mg) and a UV–visible spectrophotometric method (Ti). Copyright © 2004 John Wiley & Sons, Ltd.
A new portable XRF spectrometer with beam stability control
Authors: Romano F. P. , Calvi G. , Furia E. , Garraffo S. , Marchetta C. , Pappalardo G. , Pappalardo L. , Rizzo F. , Rovelli A.
Published: December 2004

A new portable XRF spectrometer which allows control of the energy and the intensity stability of the emitted x‐ray beam has been designed and built. The control is obtained by measuring the x‐ray fluorescence generated by a double Ag/Ba thin target when crossed by the x‐ray beam during a measurement. The silver and barium fluorescence K lines are detected by an ancillary Si‐PIN detector and analysed by software developed at the LNS/INFN laboratories. The new portable spectrometer, the beam stability control method, the evaluation of the system and some quantitative applications of interest in the cultural heritage field are presented and discussed. Copyright © 2004 John Wiley & Sons, Ltd.
Distribution of Pb and Zn in slices of human bone by synchrotron µ‐XRF
Authors: Zoeger N. , Wobrauschek P. , Streli C. , Pepponi G. , Roschger P. , Falkenberg G. , Osterode W.
Published: December 2004

Synchrotron radiation‐induced micro x‐ray fluorescence analysis (µ‐XRF) at HASYLAB beamline L was used to determine the distribution of Pb and other trace elements in slices of human bone. Using a focused synchrotron x‐ray beam of about 15 µm in diameter it was found that Pb was mostly located at the outer border of the cortical bone in various samples. Ratios of Pb intensities of cortical and trabecular bone varied from 0.027 for hip head to 0.408 for proximal tibia. Additionally Ca, Zn and Sr distributions were simultaneously recorded. A remarkable association between Pb and Zn content could be observed. Copyright © 2004 John Wiley & Sons, Ltd.
Monte Carlo study of quantitative EPMA analysis of a non‐conducting sample with a coating film
Authors: Osada Yoshio
Published: December 2004

Generally, the ZAF method has been used for quantitative electron probe microanalysis (EPMA) analysis of conducting samples. However, the ZAF method is not applied to non‐conducting samples with coating films, mainly because the x‐ray intensity and the primary electron energy are both attenuated within the coating films. In this study, for application to the ZAF method we tried to correct the x‐ray attenuation and the primary electron energy attenuation by Monte Carlo simulation. As calculation models, we selected carbon coating as a light element and gold coating as heavy element and selected four kinds of materials, Al2O3, BN, AlN and Al4C3, as non‐conducting targets. After the correction we compared the calculated results and theoretical compositions. The calculated results were in good agreement with theoretical compositions. Finally, to verify the method we measured standard Al4C3 coated with gold (100 Å thickness). The experimental result showed good agreement with the theoretical composition. In conclusion, we confirmed that this method is useful for the quantitative analysis of non‐conducting samples with coating films. Further, by combining this method with appropriate standard compounds, we can obtain the hypothetical pure x‐ray intensities of gaseous pure elements. Copyright © 2004 John Wiley & Sons, Ltd.
Frasnian plants from the Dra Valley, southern Anti-Atlas, Morocco
Authors: MEYER-BERTHAUD BRIGITTE , RÜCKLIN MARTIN , SORIA AUDE , BELKA ZDZISLAW , LARDEUX HUBERT
Published: December 2004

Anatomically preserved plant fragments are reported from Devonian marine deposits exposed in the Dra Valley of southern Anti-Atlas, Morocco. Associated conodont and tentaculite faunas indicate that the sediments yielding plants, which consist of black shales with intercalated calcareous concretions, are early Frasnian in age and most probably represent Zone 2 of the conodont zonation. This is the first record of Frasnian plants in North Africa. The specimens found all correspond to decorticated portions of axes. Six are referable to Callixylon, the organ genus corresponding to anatomically preserved axes of the progymnosperm tree Archaeopteris. Based on wood characters, especially ray structure, they are assigned to the species C. henkei, formerly described from the Famennian of Europe. One single specimen is compared to Xenocladia, a cladoxylopsid genus previously known from the Middle Devonian of Europe, USA and Kazakhstan. Interestingly, Archaeopteridales and Cladoxylopsida are two groups that dominate the younger plant assemblages of Famennian age recently described from the eastern Anti-Atlas. Callixylon henkei-type axes occur both in the Frasnian and in the Famennian deposits of the Anti-Atlas and they are all devoid of growth rings. These results are in accordance with a close position of Gondwana and Euramerica during Late Devonian times.
Pan-African extension and near-isothermal exhumation of a granulite facies terrain, Dronning Maud Land, Antarctica
Authors: ENGVIK A. K. , ELVEVOLD S.
Published: December 2004

The Mühlig-Hofmann- and Filchnerfjella in central Dronning Maud Land, Antarctica, consist of series of granitoid igneous rocks emplaced in granulite and upper amphibolite facies metamorphic rocks. The area has experienced high-temperature metamorphism followed by near-isothermal decompression, partial crustal melting, voluminous magmatism and extensional exhumation during the later phase of the late Neoproterozoic to Cambrian Pan-African event. Remnants of kyanite–garnet–ferritschermakite–rutile assemblages indicate an early higher-pressure metamorphism and crustal overthickening. The gneisses experienced peak granulite facies temperatures of 800–900 °C at intermediate pressures. Breakdown of garnet + sillimanite + spinel-bearing assemblages to cordierite shows subsequent re-equilibration to lower pressures. An E–W foliation dominating the gneisses illustrates transposition of migmatites and leucocratic melts which evolved during the near-isothermal decompression. Occurrence of extensional shear bands and shear zones evolving from the ductile partial melting stage through semiductile towards brittle conditions, shows that the uplift persisted towards brittle crustal conditions under tectonic W/SW-vergent extension. Late-orogenic Pan-African quartz syenites intruded after formation of the main gneiss fabric contain narrow semiductile to brittle shear zones, illustrating that the extensional exhumation continued also after their emplacement. The latest record of the Pan-African event is late-magmatic fluid infiltration around 350–400 °C and 2 kbar. At this stage the Pan-African crust had undergone 15–20 km exhumation from the peak granulite facies conditions. We conclude that the later phase of the Pan-African event in central Dronning Maud Land is characterized by a near-isothermal decompression P–T path and extensional structures indicating tectonic exhumation, which is most likely related to a late-orogenic collapsing phase of the Pan-African orogen.
Conodont biostratigraphy and faunal assemblages in radiolarian ribbon-banded cherts of the Burubaital Formation, West Balkhash Region, Kazakhstan
Authors: TOLMACHEVA TATIANA , HOLMER LARS , POPOV LEONID , GOGIN IVAN
Published: December 2004

Biostratigraphical study of the early to mid-Ordovician conodont fauna from ribbon-banded radiolarian cherts of the middle Burubaital Formation in Central Kazakhstan reveals an almost complete succession of conodont biozones from the late Tremadocian to the early Darriwilian. During this interval, biosiliceous sediments were deposited in basinal environments, inhabited by lingulate brachiopods, sponges, pterobranchs and caryocaridids in conditions of high fertility and primary productivity of surface water. The community structure of taxonomically diverse conodont assemblages typifying open oceanic environments is not significantly different from that of epicratonic basins of the North Atlantic conodont province. The regional increase of oxygenated bottom waters at the base of the Oepikodus evae Biozone is possibly related to considerable changes in palaeo-oceanographical circulation patterns. The finds of three natural clusters of Prioniodus oepiki (McTavish) enable us to propose an emended diagnosis of this species.
Perspectives on lithium treatment of bipolar disorder: action, efficacy, effect on suicidal behavior
Authors: Schou Mogens
Published: December 2004

Objective:

To review studies of (A) whether lithium has a prophylactic action in bipolar disorder, (B) the efficacy of prophylactic lithium treatment in comparison with the efficacy of treatment with anticonvulsant drugs, and (C) the effect of lithium treatment on suicidal behavior.

Methods:

Analysis of all relevant publications.

Results:

(A) The claim that a prophylactic action of lithium has never been satisfactorily demonstrated is based on wrong assumptions, biased selection of references, and unjustified generalizations. (B) In typical bipolar disorder lithium is significantly more efficacious than carbamazepine; in atypical bipolar disorder there is a non‐significant trend for carbamazepine to be better than lithium. Valproate has not been proven prophylactically efficacious in typical bipolar disorder; in atypical bipolar disorder it may have an effect, but it has not been compared with that of lithium. (C) A significant association has been found between prophylactic lithium treatment, on the one hand, and reduced mortality and suicidal behavior, on the other. No such association has been reported for prophylactic treatment with other mood stabilizers.

Conclusion:

In bipolar disorder the choice of prophylactic drug must be based on a weighing of efficacy against tolerability, interactions, ease of management, use during pregnancy and lactation, and expense. Lithium should be the preferred prophylactic drug in patients with typical bipolar disorder and in patients who are at high risk of committing suicide, that is, patients with severe depressions or depressions combined with persistent suicidal ideas or with suicide attempts in the past.
Topiramate as add‐on treatment for patients with bipolar mania
Authors: Roy Chengappa Kn , Rathore Dilip , Levine Joseph , Atzert Rebecca , Solai Lalith , Parepally Haranath , Levin Harry , Moffa Nicolas , Delaney Joyce , Brar Jaspreet S
Published: December 2004

Objective:

Anticonvulsant agents such as carbamazepine and valproate are alternatives to lithium in treating subjects with bipolar disorder. Topiramate (Topamax®), a new antiepileptic agent, is a candidate drug for bipolar disorder. We evaluated topiramate as adjunctive treatment for bipolar patients.

Methods:

Eighteen patients with DSM‐IV bipolar I disorder [mania (n=12), hypomania (n=1), mixed episode (n=5), and rapid cycling (n=6)], and two subjects with schizoaffective disorder – bipolar type, resistant to current mood‐stabilizer treatment were initiated on topiramate, 25 mg/day, increasing by 25–50 mg every 3–7 days to a target dose between 100 and 300 mg/day, as other medications were held constant for 5 weeks. The Young Mania Rating Scale (Y‐MRS), Hamilton Depression Rating Scale (Ham‐D), and Clinical Global Impression‐Bipolar Version Scale (CGI‐BP) were used to rate subjects weekly.

Results:

By 5 weeks, 12 (60%) subjects were responders, i.e., 50% reduction in the Y‐MRS scores and a CGI of ‘much’ or ‘very much improved’. Three subjects were ‘minimally improved’, four showed no change, and one was ‘minimally worse’. Six subjects had parasthesia, three experienced fatigue, and two had ‘word‐finding’ difficulties; in all cases, side effects were transient. All patients lost weight with a mean of 9.4 lb in 5 weeks, and a significant reduction in body mass index (BMI) occurred too.

Conclusions:

Topiramate appears to have efficacy for the manic and mixed phases of bipolar illness. Other preliminary data suggest antidepressant efficacy too. Among obese bipolar subjects, the weight loss potential of topiramate may be beneficial. If controlled trials confirm these initial results, topiramate may be a significant addition to the available treatments for bipolar disorder.
Delirious mania
Authors: Fink Max
Published: December 2004

Objectives:

To define the characteristics of delirious mania.

Methods:

A list of patients exhibiting both delirium and mania admitted to an academic psychiatric treatment unit of a tertiary care medical center was maintained for 6 years. A literature review for the terms ‘delirium’ and ‘bipolar disorder’ was undertaken.

Results:

Few articles identify the syndrome. Most cite Bell (On a form of disease resembling some advanced stages of mania and fever. Am J Insanity 1849; 6: 97–127) as the first observer and Bond (Recognition of acute delirious mania. Arch Gen Psychiatry 1980; 37: 553–554) as the most recent. Fourteen instances were identified in the case list. Delirious mania is a syndrome of the acute onset of the excitement, grandiosity, emotional lability, delusions, and insomnia characteristic of mania, and the disorientation and altered consciousness characteristic of delirium. Almost all patients exhibited signs of catatonia. Bond (1980) recommends lithium and a neuroleptic combination as the treatment. In the present series, electroconvulsive therapy was found to be safe and rapidly effective, with all cases responding within three treatments and requiring less than six treatments in the course. The rapidity of response is the same as that of patients with catatonia.

Conclusion:

Delirious mania warrants specific identification in the diagnostic nomenclature. The distinction between delirious mania and the excited or malignant forms of catatonia requires study.
Lithium isotopes: differential effects on renal function and histology
Authors: Stoll Peter M , Stokes Peter E , Okamoto Michiko
Published: December 2004

Objectives:
Reduction in renal concentrating ability has been reported in patients undergoing chronic lithium treatment. Prior work has demonstrated differences in physiological effects of the stable lithium isotopes, 6Li and 7Li. Here, we measured the degree of polyuria, polydipsia and kidney histological changes induced in rats by equimolar amounts of 6LiCl, 7LiCl and the commercially available mixture of both isotopes.   Methods: Rats were given 1.0 mEq/kg of either 6LiCl, 7LiCl or ‘nLiCl’ (isotope mixture, 93% 7LiCl) by subcutaneous injection twice daily for up to 49 days. Twenty‐four‐hour urine volume and water intake were measured daily. Kidneys from rats treated for 7 days with 1.5 mEq/kg 6LiCl, 7LiCl and vehicle were examined under light microscopy and histopathologic changes graded on a 4‐point scale of severity.   Results: All rats showed loss in renal concentrating ability manifested by increasing urine volume and water intake. Peak effects occurred after 9–13 days treatment, then declined to stable levels at two to three times pre‐treatment level. Mean peak effect was significantly greater for 6LiCl than for 7LiCl. Chronic effects of 6LiCl (weeks 3–7 of treatment) on polyuria and polydipsia were persistently higher than that of 7LiCl. nLiCl effect was intermediate. Kidneys from rats treated for 7 days with 6LiCl showed more frequently severe lesions in renal tubules than did 7LiCl‐treated rats.   Conclusions: Our current data and prior studies suggest that elimination or reduction of 6Li from pharmaceutical preparations may merit further evaluation as a possibly less potentially nephrotoxic form of lithium treatment.
Rate of switch in bipolar patients prospectively treated with second‐generation antidepressants as augmentation to mood stabilizers
Authors: Post Robert M , Altshuler Lori L , Frye Mark A , Suppes Trisha , Rush A John , Keck Paul E , McElroy Susan L , Denicoff Kirk D , Leverich Gabriele S , Kupka Ralph , Nolen Willem A
Published: December 2004

Introduction:
Bipolar patients with breakthrough major depressive episodes despite ongoing adequately‐dosed mood stabilizer medication were randomized in a double‐blind manner to one of three antidepressants with different mechanisms of action: bupropion, sertraline, or venlafaxine. Preliminary data are presented on the switch rates into hypomania or mania for the antidepressants as a group prior to unblinding the specific individual drug efficacy and tolerability data in this ongoing clinical trial.   Methods: Subjects included 64 bipolar patients who participated at five sites in a 10‐week double‐blind trial for depression and a 1‐year blinded continuation maintenance phase for responders. Nonresponders were re‐randomized such that there were 95 acute treatment phases. In the acute phase, doses were titrated to clinical response, side effects, or maximum dose of bupropion (450 mg/day), sertraline (200 mg/day), or venlafaxine (375 mg/day). Daily ratings on the National Institute of Mental Health‐Life Chart Methodology (NIMH‐LCM) were inspected for the degree of improvement on the Clinical Global Impressions scale as revised for bipolar illness (CGI‐BP) and the occurrence of hypomania or mania.   Results: Thirty‐five (37%) of the 95 acute treatment phases were associated with a much or very much improved rating in depression on the CGI‐BP. Thirteen (14%) of these 95 acute trials of antidepressants as adjuncts to mood stabilizers were associated with switches, seven into hypomania and six into mania. Forty‐two patients elected to go into the continuation phase in 48 instances. Sixteen (33%) of the continuation phase trials were associated with mood switches, 10 into hypomania and six into mania.   Conclusions: In this randomized double‐blind prospective study of three second‐generation antidepressants (bupropion, sertraline, and venlafaxine) in bipolar patients whose depression broke through ongoing treatment with mood stabilizers, switches into hypomania or mania occurred in 14% of the acute phases and 33% of the continuation phases. Individual data on each drug will be assessed in the next phase of the study after more subjects are recruited and the blind is broken.
Sleep loss and postpartum psychosis
Authors: Sharma Verinder , Mazmanian Dwight
Published: December 2004

Postpartum psychosis is a rare but severe psychiatric disorder. Its diagnostic status remains controversial, but several studies have shown that the majority of patients who develop psychosis immediately following childbirth suffer from bipolar disorder. The pathophysiology of postpartum psychosis is poorly understood, but factors such as primiparity, difficult labor, genetic predisposition, and hormonal changes have been suggested as etiological factors. This paper reviews the literature on the relationship of sleep disruption and postpartum psychosis. It is argued that sleep loss resulting from the interaction of various putative causal factors may be the final common pathway in the development of psychosis in susceptible women. Clinical significance of these findings, including strategies to prevent postpartum psychosis, are discussed and suggestions are made for future research directions.
Social support in bipolar disorder: its relevance to remission and relapse
Authors: Johnson Lars , Lundström Ola , Åberg‐Wistedt Anna , Mathé Aleksander A
Published: December 2004

Objectives:  While an association between low‐level social support and depression has been found in many studies, its relevance in bipolar illness has been rarely investigated. The aim of this study was to investigate the effects of social support in the remission and relapse of bipolar disorder.

Methods:  We obtained ratings from 94 stabilized bipolar patients using two different questionnaires that measure perceived social support: the Interview Schedule for Social Interaction and the Interpersonal Support Evaluation List.

Results:  Significantly lower social support was found in patients in partial recovery compared with those in full recovery (p = 0.003). Patients who relapsed during a 1‐year prospective follow‐up period perceived a significantly lower level of social support than patients with no relapse (p = 0.012).

Conclusions:  Bipolar patients with full interepisode remission perceive more social support than those who do not achieve full remission. Poor social support may increase the risk of relapse in bipolar disorder.
Response of patients with panic disorder and symptoms of hypomania to cognitive behavior therapy for panic
Authors: Bowen Rudy C , D'Arcy Carl
Published: December 2004

Objectives:  The purpose of this cohort study was to determine in patients with Panic Disorder (PD): (1) the prevalence of subsyndromal symptoms of hypomania, and (2) whether subsyndromal hypomania symptoms affect the outcome of cognitive behavior therapy (CBT) for panic.

Methods:  Using the Diagnostic Interview Schedule, and DSM‐III‐R criteria we identified 18 individuals with a history of symptoms of hypomania among 56 patients with PD. Patients were treated in an open CBT group program. They were assessed before treatment and 6 and 12 months later. We used the Brief Symptom Inventory (BSI), the Perceived Stress Scale (PSS), the Pearlin‐Schooler Mastery Scale (PMS), and the Social Adjustment Scale (SAS) at all assessments.

Results:  The total group significantly improved on all measures. The Clinically Significant Change was 71.4% and the Reliable Change Index 48.2%. Between 6 and 12 months, there was a trend for the hypomania symptom subgroup (PH) to continue to improve on the BSI Depression Scale, the Perceived Stress Scale, the Pearlin–Schooler Mastery Scale, and the Social Adjustment Scale but to lose gains on the BSI Phobic Anxiety and Somatization subscales compared with the group without symptoms of hypomania (PNH).

Conclusions:  Thirty‐two percent of patients with PD had symptoms of hypomania. With CBT for panic, patients with PD and symptoms of hypomania improve as much as those without hypomania symptoms. The presence or absence of symptoms of hypomania might help explain the inconsistent effects of depression and personality disorders on the treatment of PD.
Impaired heart rate variability in euthymic bipolar patients
Authors: Cohen Hagit , Kaplan Zeev , Kotler Moshe , Mittelman Irena , Osher Yamima , Bersudsky Yuly
Published: December 2004

Background:  Power spectral analysis of heart rate variability (HRV) has recently been shown to be a reliable non‐invasive test for quantitative assessment of the central sympathovagal interaction that modulates cardiovascular autonomic function.

Methods:  We studied 39 euthymic bipolar patients and 39 controls, matched for age and sex. A high‐resolution electrocardiogram was obtained during complete rest. Spectral analysis of R–R intervals was performed by the fast Fourier transform algorithm.

Results:  Euthymic bipolar patients at rest are characterized by markedly low HRV, independent of specific drug treatments.

Conclusion:  While these results of autonomic stability in euthymic bipolar patients are counter‐intuitive, the findings may be important in understanding pathophysiology of bipolar affective illness.
The comorbidity of bipolar disorder and axis II personality disorders: prevalence and clinical correlates
Authors: George Elizabeth L , Miklowitz David J , Richards Jeffrey A , Simoneau Teresa L , Taylor Dawn O
Published: December 2004

Objectives:  Many studies have examined the prevalence and predictive validity of axis II personality disorders among unipolar depressed patients, but few have examined these issues among bipolar patients. The few studies that do exist suggest that axis II pathology complicates the diagnosis and course of bipolar disorder. This study examined the prevalence of axis II disorder in bipolar patients who were clinically remitted.

Methods:  We assessed the co‐occurrence of personality disorder among 52 remitted DSM‐III‐R bipolar patients using a structured diagnostic interview, the Personality Disorder Examination (PDE).

Results:  Axis II disorders can be rated reliably among bipolar patients who are in remission. Co‐diagnosis of personality disorder occurred in 28.8% of patients. Cluster B (dramatic, emotionally erratic) and cluster C (fearful, avoidant) personality disorders were more common than cluster A (odd, eccentric) disorders. Bipolar patients with personality disorders differed from bipolar patients without personality disorders in the severity of their residual mood symptoms, even during remission.

Conclusions:  When structured assessment of personality disorder is performed during a clinical remission, less than one in three bipolar patients meets full syndromal criteria for an axis II disorder. Examining rates of comorbid personality disorder in broad‐based community samples of bipolar spectrum patients would further clarify the linkage between these sets of disorders.
Population pharmacokinetics of clomethiazole and its effect on the natural course of sedation in acute stroke patients
Authors: Zingmark Per‐Henrik , Ekblom Marianne , Odergren Tomas , Ashwood Tim , Lyden Patrick , Karlsson Mats O. , Jonsson E. Niclas
Published: December 2004

Aims   This analysis was performed to investigate the population pharmacokinetics of clomethiazole and its effect on the natural course of sedation in acute stroke patients using a nonlinear mixed effects modelling approach.

Methods   One thousand five hundred and forty‐six acute stroke patients (774 on active treatment) from 166 centres were included in three randomized, double‐blind, placebo‐controlled phase III efficacy and safety studies. A total dose of 68 mg kg−1 clomethiazole edisilate was given as a three‐phase i.v.‐infusion over 24 h. Three blood samples were drawn from all patients to characterize the pharmacokinetics. Sedation was monitored throughout the entire treatment period and the degree of sedation was measured on a discrete ordinal scale with six levels. Models were fitted to the data using the software NONMEM.

Results   Clomethiazole was characterized by a two‐compartment pharmacokinetic model with interindividual variability in all structural parameters. For a patient weighing 75 kg, the average CL, V1, Q, and V2 was estimated to be 52.7 l h−1, 82.5 l, 167 l h−1 and 335 l, respectively. The interindividual variability in CL, V1, Q and V2 was estimated to be 48%, 53%, 42% and 54%, respectively. Increasing body weight and concomitant administration of liver enzyme inducing drugs were found to increase clearance (by 0.5 l h−1 kg−1 and 40%, respectively). Increasing weight also increased the volume of distribution (1.1 l kg−1 for V1 and 4.7 l kg−1 for V2). A six‐category proportional odds model with a component including the natural course of sedation following placebo administration, a drug component (present or absent) and an interindividual variability component described the degree of sedation. Stroke severity as measured on the NIH‐stroke scale on admission and drug treatment were the most important predictors of sedation, but a nonlinear increase in sedation with increasing age was also found. Increasing body weight increased the sedative drug effect.

Conclusions   The pharmacokinetics of clomethiazole were characterized in acute stroke patients and the analysis excluded several possible covariates of interest in drug development. The time course of sedation could be quantitatively described during the first 24 h following an acute stroke in the presence or absence of clomethiazole treatment.
A simple pain model for the evaluation of analgesic effects of NSAIDs in healthy subjects
Authors: Sycha Thomas , Gustorff Burkhard , Lehr Stephan , Tanew Adrian , Eichler1 Hans‐Georg , Schmetterer Leopold
Published: December 2004

Aims  Non‐steroidal anti‐inflammatory drugs (NSAIDs) are believed to counteract inflammation and inflammation‐induced sensitization of nociceptors by inhibiting peripheral prostaglandin synthesis. We evaluated an experimental pain model for NSAIDs, that included an inflammatory component to mimic clinical inflammatory pain conditions.

Methods  The study was performed in a randomized, double‐blind, placebo‐controlled, two‐way crossover design on 32 healthy volunteers. A small skin area of the proximal upper leg was irradiated with a UVB source using three times the individually estimated minimal erythema dose. Twenty hours after irradiation skin temperature, heat pain threshold and tolerance in sunburn spot were measured using a thermal sensory testing. These measurements were repeated 2 h after medication of either 800 mg ibuprofen as single oral dose or placebo capsules. Effects of ibuprofen on outcome parameters were assessed with analyses of covariance (ancova).

Results  Placebo did not affect heat pain threshold or tolerance. By contrast, ibuprofen increased heat pain threshold by 1.092 °C [confidence interval (CI) 0.498, 1.695; P = 0.0008) compared with placebo. Heat pain tolerance also increased significantly by 1.618 °C (CI 1.062, 2.175; P = 0.0001).

Conclusion  The pain model we evaluated was well tolerated in all subjects and the effects of ibuprofen were highly significant. This model is simple, sensitive to NSAIDs’ effects and therefore has potential for future experimental pain studies.
Maintenance of pregnancy in ovariectomized Mongolian gerbils (Meriones unguiculatus)
Authors: KAI Osamu , MATSUMOTO Naeko , TAKINOSAWA Miho , SONODA Yutaka
Published: December 2004

Bilateral ovariectomy (Ovx) was carried out on day 20 of pregnancy in Mongolian gerbils (Meriones unguiculatus). The body weights of all groups tended to decrease on the day after the operation, and the decrease was significant in the group that was ovariectomized and given vehicle (Ovx + vehicle group). The body weight in this group never recovered until autopsy on day 24, which is normally 1 day before parturition. No fetuses survived to the time of autopsy in any of the animals of the Ovx + vehicle group. Daily administration of 4 mg of progesterone (P4) prevented the termination of pregnancy in Ovx animals, but 1 mg did not. Treatment with estradiol 17β (E2) in addition to 4 mg of P4 tended to result in a lower rate of fetal survival than that of the Ovx group treated with 4 mg of P4 alone. With regard to fetal weight, treatment with 4 mg of P4 resulted in the same weight as in the sham‐operated controls, but the addition of 0.2 or 1 μg of E2 to the 4 mg of P4 resulted in a significantly lower weight than that of fetuses in the 4 mg of P4 group. The present study suggests that adequate maintenance of pregnancy in ovariectomized gerbils can be achieved by daily treatment with 4 mg of P4 alone. Moreover, treatment with 0.2 or 1 μg of E2 in addition to 4 mg of P4 caused a deterioration in the maintenance of gestation, in contrast to the effects in rats, mice and hamsters.
Sequential expression of myogenic regulatory factors in bovine skeletal muscle and the satellite cell culture
Authors: MUROYA Susumu , NAKAJIMA Ikuyo , CHIKUNI Koichi
Published: December 2004

Myogenic regulatory factors (MRFs) are important in the control of skeletal muscle development. To understand myogenic regulation by MRFs in bovine adult muscle cells, their expressions, namely that of Myf5, MyoD, myogenin, and MRF4 in the biceps femoris muscle (BF) and in the satellite cell culture, were analyzed by RT‐PCR. In the BF, all four MRFs were expressed and in particular, myogenin and MRF4 were strongly expressed, whereas Myf5 was faintly expressed. The satellite cells prepared from the BF expressed Myf5, but only a trace of MyoD, at day 9 of culture. During the growth of the cells to day 14, the MyoD and myogenin expressions gradually increased, and that of MyoD expression reached its maximum at the confluence of the culture. After induction of myogenic differentiation by a serum‐free medium at day 14, Myf5 expression gradually decreased, and the up‐regulated expression of MyoD was suppressed, whereas myogenin expression continued to increase sharply. Following the myogenin expression, MRF4 also drastically increased toward the myotube formation of the cells. When huge myotubes were formed at day 18, Myf5 was expressed at a low level, whereas the MyoD expression remained at a moderate level.
Factors affecting agonistic interactions of pigs after regrouping in pens with a box
Authors: ISHIWATA Toshie , UETAKE Katsuji , TANAKA Toshio
Published: December 2004

To determine the factors affecting agonistic interactions after regrouping, 24 pigs were allocated to six pens that each had a box. Half of the pigs were experienced in using the box. One castrated male and one female pig were transferred from each pen to another pen at random. The number of pigs attacked was particularly large for the pigs that had no experience in using the box and were transferred on the first day (P < 0.05). The duration of access to the box was markedly longer for the pigs that had experience in using the box and were not transferred on the first day (P < 0.05). The number and duration of attacks were significantly larger and longer toward unfamiliar individuals than toward familiar ones (both P< 0.01). The number of attacks toward the same sex was significantly larger than toward the opposite sex (P < 0.01). A negative correlation was found between the number of agonistic interactions on the first day and the range of body weights in the pen mates (r = −0.78, P = 0.07). In conclusion, regrouping with unfamiliar individuals should be avoided, but when unavoidable, the following methods are recommended to reduce agonistic interactions: (1) ensure the intruders are experienced in using a box, (2) move experienced intruders in with residents that have no experience in using a box, (3) mix different sexes, and (4) have wide variations in body weights in a pen.
Influence of transgenic corn (CBH 351, named Starlink) on health condition of dairy cows and transfer of Cry9C protein and cry9C gene to milk, blood, liver and muscle
Authors: YONEMOCHI Chisato , IKEDA Takuo , HARADA Chisato , KUSAMA Toyoko , HANAZUMI Michito
Published: December 2004

The influence of transgenic event CBH 351 (Starlink)‐derived hybrid corn (SL) on the health condition, physiological function and lactational performance of dairy cows as well as the transfer of the cry9C gene and Cry9C protein present in SL to milk, blood, liver and muscles was examined, and compared with a diet containing non‐transgenic (isogenic) control corn (non‐SL). After adapting to a diet containing non‐SL for 2 weeks, four Holstein cows were assigned to each of the non‐SL and SL groups and were fed diets containing non‐SL or SL, respectively, for 5 weeks. There were no significant influences on the physiological condition, milk yield or serum biochemical and hematological values after feeding with SL. There was also no influence on pH value, cell density of protozoa, or volatile fatty acid concentration and composition of rumen fluids. In addition, no significant differences were observed on histopathological examination of the major organs and tissues between the SL and non‐SL groups. Moreover, the cry9C gene and Cry9C protein were not detected by the polymerase chain reaction method and ELISA in the milk, blood, liver and muscles of the cows at the end of the experiment.