bluuebunny/crossref_metadata_2025 huggingface dataset:
New Starch Phosphate Carbamides of High Swelling Ability: Synthesis and Characterization
Authors: Heinze Ute , Klemm Dieter , Unger Ekkehard , Pieschel Friedemann
Published: February 2003

The paper describes the synthesis of starch phosphate carbamides by reacting starch with phosphoric acid and urea. A solid state technique in vacuum at elevated temperatures is used. The degree of substitution of phosphate (DSP) and carbamide groups (DSC) can be adjusted by the molar ratio of starch: phosphoric acid: urea, the reaction temperature, and time. The starch derivatives prepared show remarkable swelling if the DSP ranges between 0.2 and 0.3. With increasing content of urea in the reaction mixture the water‐holding ability is still significantly improved, which is explained by chemically and especially physically introduced urea into the starch polymer. Furthermore, the ratio of amylose: amylopectin of the starch samples influences both the DS values and the physicochemical properties, e.g., swelling power and multivalent metal ion adsorption of the products.

The structure of the new polymers was determined by means of FTIR, 13C‐ and 31P NMR spectroscopy as well as by gel permeation chromatography (GPC).
Granule Integrity and Starch Solubility During Slow, Extended Pasting of Maize Starch — the Second Viscosity Peak
Authors: Nelles Elizabeth M. , Dewar Janice , van der Merwe Chris F. , Taylor John R. N.
Published: February 2003

Maize starch granule integrity and starch solubilisation at specific intervals during a relatively long pasting profile—which is known to exhibit biphasic peak viscosity character—was studied by microscopy and high‐performance size‐exclusion chromatography, respectively. Maize starch granules, although swelling and leaching components, remained mainly intact until the second viscosity peak when they lost integrity and formed a relatively homogenous paste. The second viscosity peak coincided with a decrease in starch content in solution and amylose going out of solution was mainly responsible for this decrease. It is suggested that the loss of granule integrity during the second viscosity peak increases the potential for amylose to form complexes with lipids at this stage. It is further suggested that the second viscosity peak is due to the formation and breakdown of superstructures of amylose‐lipid complexes.
Material Properties and Glass Transition Temperatures of Different Thermoplastic Starches After Extrusion Processing
Authors: de Graaf Robbert A. , Karman Andre P. , Janssen Léon P. B. M.
Published: February 2003

Four different starch sources, namely waxy maize, wheat, potato and pea starch were extruded with the plasticizer glycerol, the latter in concentrations of 15, 20 and 25% (w/w). The glass transition temperatures of the resulting thermoplastic products were measured by Dynamic Mechanical Thermal Analysis (DMTA). Beside mechanical and structural properties also the transition temperatures of the materials were evaluated during tensile and impact tests. Above certain glycerol contents, dependent on the starch source, a lower glass transition temperatureTgresulted in decreased modulus and tensile strengths and increased elongations. Lowering theTgat different glycerol contents did not influence the impact strength. When the amylose/amylopectin ratio increased a decrease inTgwas found. For pea, wheat, potato and waxy maize starch theTgwas 75 °C, 143 °C, 152 °C and 158 °C, respectively. Therefore products with higher percentages of amylose are more flexible. The shrinkage of the specimens made by injection molding was considerable compared to the specimens made by pressing.
A New Sulfato‐bridged Manganese(II) Phenanthroline Complex: [Mn(phen)(H2O)2(SO4)]
Authors: Zheng Yue‐Qing , Lin Jian‐Li
Published: February 2003

The sulfato bridged MnII phen complex [Mn(phen)(H2O)2SO4] (4) consists of [Mn(H2O)2(phen)(SO4)2/2] chains, which are generated from Mn atoms in distorted octahedral sites interlinked by bidentate sulfato bridges. Interdigitation of phen ligands leads to the formation of [Mn(H2O)2(phen)(SO4)2/2] double‐chains stabilized by significant π—π stacking interactions. The double‐chains are held together via interchain hydrogen bonds formed between water and sulfato O atoms. Crystal data: orthorhombic, P212121 (no. 19), a = 6.674(1), b = 10.359(1), c = 19.913(3)Å, V = 1376.7(3)Å3, Z = 4, R = 0.0439 and wR2 = 0.0935 for 1830 out of 2286 reflections with Fo2 > 2σ(Fo2).
Bildung und Kristallstruktur eines dimeren sauerstoffverbrückten Titanaminobisphenoxides
Authors: Baldamus Jens , Hecht Elmar
Published: February 2003

Formation and Crystal Structure of an Oxygen Bridged Titanium Amino Bisphenoxide

Di‐(μ‐oxo)‐titan‐bis[aminobisphenoxide] (3) was obtained by reaction of (i‐Prop)2TiL* (2) {L* = O‐4, 6‐(t‐Bu)2C6H2‐2‐CH2‐[1, 4‐N2C5H10]‐2'‐CH2‐4', 6'‐(t‐Bu)2C6H2O] with water in a molar ratio 1:1 in diethylether. Both i‐Propyl moieties are substituted yielding the dimeric oxygen bridged amino bisphenoxide complex. The six coordinate Ti atoms are a result of Ti—N and Ti—O interactions of the corresponding atoms of the amino bisphenoxide ligand and the bridging O atoms. The central planar Ti2O2 ring may be considered as the general structural feature of the title compound: Space group P1¯, Z = 1, lattice dimensions at —60°C: a = 11.6899(4), b = 11.7873(4), c = 12.6462(4) Å, α = 98.070(1), β = 99.660(1), γ = 95.343(1)°, R1 = 0.0469, wR2 = 0.1049, GooF = 0.939.
Neue Gold‐Selen‐Komplexverbindungen: Synthesen und Strukturen von [Au10Se4(dpppe)4]Br2, [Au2Se(dppbe)]∞, [(Au3Se)2(dppbp)3]Cl2 und [Au34Se14(tpep)6(tpepSe)2]Cl6
Authors: Sevillano Paloma , Langetepe Timo , Fenske Dieter
Published: February 2003

Die Umsetzung von Gold‐Phosphan‐Komplexen [(AuX)(PR3)] (X= Halogen; R = org. Rest) mit Se(SiMe3)2 führt zu neuen chalkogenoverbrückten Goldkomplexen. Durch die Verwendung mehrzähniger Phosphanliganden konnten Clusterkomplexe wie [Au10Se4(dpppe)4]Br2 (1) (dpppe = 1, 5‐Bis (diphenylphosphino)pentan), [Au2Se(dppbe)]∞ (2) (1, 4‐Bis(diphenylphosphino)benzol), [(Au3Se)2(dppbp)3]Cl2 (3) (dppbp = 4, 4′‐Bis(diphenylphosphino)biphenyl) und [Au34Se14(tpep)6(tpepSe)2]Cl6 (4) (tpep = 1, 1, 1‐Tris(diphenylphosphino)ethylphosphan, tpepSe = 1, 1‐Bis‐(di‐phenylphosphinoethyl)‐1‐(diphenylselenophosphinoethyl)phosphan) isoliert und deren Struktur mit Hilfe der Einkristallstruktur‐Analyse bestimmt werden (Strukturdaten s. Abstract).
Naphtholactam als Komplexligand
Authors: Limmert Michael , Lorenz Ingo‐Peter , Neubauer Jürgen , Schulz Axel , Piotrowski Holger
Published: February 2003

Nach Überführung des Fluorophors N‐Benz[cd]indol‐2(1H)‐on (= Naphtholactam) mit NaN(SiMe3)2 in das Naphtholactamat 1 und Umsetzung mit den Chlorokomplexen [Ph3PAuCl] und [(Ph3P)2PtCl2] entstehen die Mono‐ bzw. Disubstitutionsprodukte [Ph3PAu(C11H6NO)] (2), [(Ph3P)2PtCl(C11H6NO)] (3) und [(Ph3P)2Pt(C11H6NO)2] (4) mit einer bzw. zwei Metall‐N‐Bindungen. Bei der Umsetzung von 1 mit den Chlorophosphanen Ph3‐nPCln bilden sich die Naphtholactamato‐N‐phosphane Ph3‐nP(C11H6NO)n (n = 3 (5), 2 (6), 1 (7)), von denen sich insbesondere 7 durch Luftsauerstoff zum Phosphanoxid Ph2P(O)(C11H6NO) (8) oxidieren läßt. Die Ligandeneigenschaften der neuen Phosphane werden überprüft. Ausgehend von HAuCl4, C4H8S (= THT) und 7 entsteht der Phosphankomplex [{Ph2(C11H6NO)P}AuCl] (9). W(CO)6 setzt sich nach photolytischer CO‐Eliminierung mit 5 bzw. 7 zu den Tetracarbonyl‐Komplexen $[(CO)_{4}\overline{W\{P(C_{11}H_{6}NO)_{2}(C_{11}H_{6}NO)\}]}$/ (10) bzw. $[(CO)_{4}\overline{W\{PPh_{2}(C_{11}H_{6}NO)\}]}$/ (11) mit zweizähnig P, O‐gebundenden Naphtholactamatophosphan‐Liganden um. Die Verbindungen wurden IR‐, NMR‐ und MS‐spektroskopisch charakterisiert, 11 zusätzlich durch eine Einkristall‐Röntgenstrukturanalyse. Bei 5 wurden Berechnungen auf PM3‐Niveau zur Strukturoptimierung sowie eine NBO‐Analyse durchgeführt.
Copper(II) Polyamine Complexes with N‐Benzothiazole Sulfonamides as Counterions — Synthesis, Crystal Structures, and Properties of [Cu(dien)2](L1)2[HL1 = N‐2‐(benzothiazole)naphtalenesulfonamide, dien = diethylentriamine] and [Cu(en)2(H2O)2](L2)2[HL2 = N‐2‐(6‐chlorobenzothiazole)toluenesulfonamide, en = ethylenediamine] — Superoxide Dismutase‐like Activity
Authors: González‐Álvarez Marta , Alzuet Gloria , Borrás Joaquín , Macías Benigno , Montejo‐Bernardo Jose Manuel , García‐Granda Santiago
Published: February 2003

Copper(II) complexes of new N‐benzothiazole sulfonamides (HL1= N‐2‐(benzothiazole)naphtalensulfonamide and HL2 = N‐2‐(6‐chlorobenzothiazole)toluenesulfonamide) with ethylenediamine (en) and diethylenetriamine (dien) have been synthesized and characterised. The crystal structures of [Cu(dien)2](L1)2 (1) and [Cu(en)2(H2O)2](L2)2 (2) compounds have been determined. The metal centre adopts a “4+2” distorted octahedral environment in both complexes. Unusually, the sulfonamidate anions act as counterions. Spectroscopic properties are in good agreement with the crystal structures. The superoxide dismutase (SOD)‐like activity of complex 2 has been tested.
Evidence of a Photo‐Radical Pathway Responsible of the Rearrangement of a Manganese(III)‐Schiff Base Complex in Solution
Authors: Maneiro Marcelino , Bermejo Manuel R. , Fernández M. Isabel , González‐Noya Ana M. , Tyryshkin Alexei M. , Pritchard Robin G.
Published: February 2003

A new MnIII‐Schiff base complex, [MnL(OH2)](ClO4) (1) (H2L = N, N′‐bis‐(3‐Br‐5‐Cl‐salicylidene)‐1, 2‐diimino‐2‐methylethane), an inorganic model of the catalytic center (OEC, Oxygen Evolving Complex) in photosystem II (PSII), has been synthesized and characterized by elemental analysis, IR and EPR spectroscopy, mass spectrometry, magnetic susceptibility measurement and the study of its redox properties by cyclic and normal pulse voltammetry. This complex mimics reactivity (showing a relevant photolytic activity), and also some structural characteristics (parallel‐mode MnIII EPR signal from partially assembled OEC cluster) of the natural OEC. The complex 1 was found to rearrange in solution into a crystallographically solved square‐pyramidal complex, [MnLL′] (2) (HL′ = 6‐bromo‐4‐chloro‐2‐cyanophenol), through a process, which probably liberates radical species (detected by EPR), and provokes a C—N bond cleavage in the ligand. A photo‐radical mechanism is discussed to explain this rearrangement.
Synthesis, Crystal Structure and Properties of [Cu(phen)3][Cu(pheida)2]·10H2O and [(phen)2Cu(μ‐BAAP)Cu(μ‐BAAP)Cu(phen)2][Cu(BAAP)2]·8.5H2O (H2pheida = N‐phenetyl‐iminodiacetic acid, H2BAAP = N‐benzylaminoacetic‐2‐propionic acid)
Authors: Choquesillo‐Lazarte D. , Sánchez‐Moreno M.J. , Bugella‐Altamirano E. , Moyano‐Gallego M. J. , Martín‐Ramos J. D. , González‐Pérez J. M. , Carballo R. , Niclós‐Gutiérrez J.
Published: February 2003

The salts [Cu(phen)3][Cu(pheida)2]·10H2O (1) and [(phen)2Cu(μ‐BAAP)Cu(μ‐BAAP)Cu(phen)2][Cu(BAAP)2]·8.5H2O (2) (H2pheida = N‐phenetyl‐iminodiacetic acid, H2BAAP = N‐benzylaminoacetic‐2‐propionic acid, phen = 1, 10‐phenanthroline) have been prepared and studied by thermal, spectroscopic and X‐ray diffraction methods. 1 has the rather unusual [Cu(phen)3]2+ cation and two non‐equivalent [Cu(pheida)2]2— anions with a coordination type 4+2 but quite different tetragonality (T = 0.848 and 0.703 for anions 1 and 2, respectively). The crystal consists of multi‐π, π‐stacked chains (…anion 2 — cation — cation — anion 2…) connected by hydrophobic interactions; these chains build channels which are partially filled by anions 1 and water molecules. In contrast, compound 2 has a mixed‐ligand trinuclear cation with a bridging central moiety close similar to the counter anion. The formation of such a trinuclear cation is discussed as a consequence of the most advantageous molecular recognition process between [Cu(phen)2(H2O)1 or 2]2+ and [Cu(BAAP)2]2— in solution. In the crystal of 2, multi‐π, π‐stacked arrays of C6‐rings from phen and (BAAP)2— ligands of trinuclear cations generate channels where counter anions and water molecules are located.
Silsesquioxane Chemistry. 12 [1] Preparation and Complexation of a Novel Silsesquioxanyl Phosphine Ligand
Authors: Fei Zhaofu , Schmutzler Reinhard , Edelmann Frank T.
Published: February 2003

The reaction of the monofunctional closo‐silsesquioxane silanol derivative Cy7Si8O12OH (3, Cy = c‐C6H11) with tris(dimethylamino)phosphine afforded the novel silsesquioxanyl phosphine ligand Cy7Si8O12OP(NMe2)2 (4) in virtually quantitative yield. The complexes [Cy7Si8O12OP(NMe2)2]2PtCl2 (5) and [Cy7Si8O12OP(NMe2)2]2Mo(CO)4 (6) were obtained in excellent yields upon treatment of 4 with (COD)PtCl2 (COD = 1, 5‐cyclooctadiene) and (NBD)Mo(CO)4 (NBD = norbornadiene), respectively. An attempted preparation of the bis(silsesquioxanyl)phosphine (Cy7Si8O12O)2P(NMe2) led to the formation of the known disiloxane derivative (Cy7Si8O12)2O (7), instead.
Anti-parasitic effect of cyclosporin A on Echinococcus granulosus and characterization of the associated cyclophilin protein
Authors: COLEBROOK A. L. , JENKINS D. D. , LIGHTOWLERS M. W.
Published: February 2003

Cyclophilins are a family of proteins found ubiquitously in eukaryotes, many of which bind to the immunosuppressive drug cyclosporin A (CsA). CsA has been found to have anti-parasitic effects against a variety of helminth and protozoan parasites and this activity could be mediated via cyclophilin. In this study we characterize a full length cyclophilin gene from Echinococcus granulosus, the associated natural gene and expression pattern, and investigate the functional properties of the recombinant E. granulosus cyclophilin protein. In addition, the effects of CsA were investigated on E. granulosus protoscoleces in in vitro culture. The full length E. granulosus cyclophilin cDNA encodes a protein of 20 kDa and is encoded by a single gene (EGCyP-1) comprising 2 exons separated by a 31 bp intron. The gene is expressed constitutively in all E. granulosus life-cycle stages examined. Recombinant E. granulosus cyclophilin (egCyP-1) exhibited functional enzyme activity as an isomerase. Treatment of in vitro cultures of E. granulosus protoscoleces with CsA was found to be lethal to the parasites. No protoscoleces survived treatment with 10 μg/ml of CsA over 7 culture days, as determined by observing motility and the uptake of toluidine blue dye. Untreated protoscoleces remained viable for the duration of experiments. The survival of protoscoleces was CsA dose dependent. A concentration of 10 μg/ml CsA was 100% lethal while doses of 8 μg/ml and 5 μg/ml resulted in 82% and 32% killing, respectively, after 7 days in culture. The anti-parasitic activity of CsA may have the potential to be developed as a new therapeutic agent for treatment of cystic hydatidosis in humans.
Behavioural phenotypes associated with specific genetic disorders: evidence from a population-based study of people with Prader-Willi syndrome
Authors: HOLLAND A. J. , WHITTINGTON J. E. , BUTLER J. , WEBB T. , BOER H. , CLARKE D.
Published: February 2003

Background. Prader-Willi syndrome (PWS) is a genetic disorder resulting in obesity, short stature, cryptorchidism, learning disabilities (mental retardation) and severe neonatal hypotonia. Associated with the syndrome are a number of behaviours that are sufficiently distinctive that the syndrome is considered to have a specific ‘behavioural phenotype’.

Methods. Through multiple sources we attempted to identify all people with PWS living in one region in the UK. This cohort was augmented by people with PWS from other regions, and a contrast group of people with learning disabilities of varied aetiologies. The main carers were interviewed, using structured and semi-structured interview schedules, to establish the presence and severity of specific behaviours, and PWS diagnostic criteria. The intellectual functioning and attainments of all were determined. Blood samples were obtained for genetic diagnosis from all consenting participants.

Results. Although excessive eating was recognized as a potentially severe problem in those with PWS, it was almost universally controlled by food restriction, and therefore not seen as a ‘problem behaviour’. Those with PWS differed from a learning disabled group of other aetiologies in the prevalence rates of skin picking, temper tantrums, compulsive behaviours and mood fluctuations, and also in the profile of their adaptive behaviours.

Conclusions. The study confirms the distinct behavioural phenotype of PWS. Specific behaviours occurred significantly more frequently in PWS, compared with an age and BMI matched learning disabled comparison group. A factor analysis of the behaviours involved resulted in three factors that we hypothesized to be independent, and to arise from different mechanisms.
Vulnerability and resiliency to suicidal behaviours in young people
Authors: FERGUSSON D. M. , BEAUTRAIS A. L. , HORWOOD L. J.
Published: February 2003

Background. We aimed to examine factors that influence vulnerability/resiliency of depressed young people to suicidal ideation and suicide attempt.

Method. Data were gathered during a 21-year longitudinal study of a birth cohort of 1265 New Zealand young people. Measures included: suicide attempt; suicidal ideation; major depression; childhood, family, individual and peer factors.

Results. Young people who developed major depression had increased rates of suicidal ideation (OR=5·4; 95% CI 4·5–6·6) and suicide attempt (OR=12·1; 95% CI 7·9–18·5). However, the majority of depressed young people did not develop suicidal ideation or make suicide attempts, suggesting that additional factors influence vulnerability or resiliency to suicidal responses. Factors influencing resiliency/vulnerability to suicidal responses included: family history of suicide; childhood sexual abuse; neuroticism; novelty seeking; self-esteem; peer affiliations; and school achievement. These factors operated in the same way to influence vulnerability/resiliency among those depressed and those not depressed.

Conclusions. Vulnerability/resiliency to suicidal responses among those depressed (and those not depressed) is influenced by an accumulation of factors including: family history of suicide, childhood sexual abuse, personality factors, peer affiliations and school success. Positive configurations of these factors confer increased resiliency, whereas negative configurations increase vulnerability.
Insight: its relationship with cognitive function, brain volume and symptoms in schizophrenia
Authors: ROSSELL S. L. , COAKES J. , SHAPLESKE J. , WOODRUFF P. W. R. , DAVID A. S.
Published: February 2003

Background. Lack of insight is frequently observed in schizophrenia. Relationships have been noted between poor insight, clinical symptoms and cognitive impairments but the findings are inconsistent. There have been some recent attempts to relate poor insight to neuro-anatomical measures.

Method. We assessed insight, positive and negative symptoms of schizophrenia, cognitive performance, and whole brain volumes in a sample of 78 DSM-IV male schizophrenics and 36 normal male comparison subjects matched for age and IQ. Subjects underwent a dual-echo MRI brain scan to establish grey, white and whole brain volumes.

Results. Poor Wisconsin Card Sorting Test performance inversely correlated with insight in schizophrenic patients, as did the symptoms alogia, anhedonia, avolition/apathy, affective flattening, inappropriate affect, thought disorder and delusions. The presence of inappropriate affect, delusions and thought disorder, showed the most significant impact on insight levels. There were no significant correlations between whole brain, white and grey matter volume and degree of insight.

Conclusions. The results suggest that poor insight is significantly related to schizophrenic psychopathology, and confirm that there is a relationship between insight and executive performance. Awareness of illness is not related to any global brain measures, suggesting future investigations should pay attention to more specific cortical regions such as the frontal cortex.
Factors associated with the wish to hasten death: a study of patients with terminal illness
Authors: KELLY B. , BURNETT P. , PELUSI D. , BADGER S. , VARGHESE F. , ROBERTSON M.
Published: February 2003

Background. There is considerable debate regarding the clinical issues surrounding the wish to hasten death (WTHD) in the terminally ill. The clinical factors contributing to the WTHD need further investigation among the terminally ill in order to enhance understanding of the clinical assessment and treatment needs that underlie this problem. A more detailed understanding may assist with the development of appropriate therapeutic interventions.

Method. A sample of terminally ill cancer patients (N=256) recruited from an in-patient hospice unit, home palliative care service and a general hospital palliative care consulting service from Brisbane Australia between 1998–2001 completed a questionnaire assessing psychological (depression and anxiety), social (family relationship, social support, level of burden on others) and the impact of physical symptoms. The association between these factors and the WTHD was investigated.

Results. A high WTHD was reported by 14% of patients. A discriminant function analysis revealed that the following variables were associated with a high WTHD (P<0·001): higher levels of depressive symptoms, being admitted to an in-patient hospice setting, a greater perception of being a burden on others, lower family cohesion, lower levels of social support, higher levels of anxiety and greater impact of physical symptoms.

Conclusions. Psychological and social factors are related to a WTHD among terminally ill cancer patients. Greater attention needs to be paid to the assessment of psychological and social issues in order to provide appropriate therapeutic interventions for terminally ill patients.
The health effects of peace-keeping in the UK Armed Forces: Bosnia 1992–1996. Predictors of psychological symptoms
Authors: HOTOPF M. , DAVID A. S. , HULL L. , ISMAIL K. , PALMER I. , UNWIN C. , WESSELY S
Published: February 2003

Background. Peace-keeping duties are associated with unique stresses for military personnel. There have been few reports on the effects of peace-keeping on psychological health.

Method. We used data from a cross-sectional study originally established to examine health effects of service in the Gulf War, which included a control group who had been deployed in Bosnia (N=2049). This group was examined to establish which demographic, occupational, and deployment-related risk factors were associated with psychological distress measured on the General Health Questionnaire (GHQ-12) and stress symptoms akin to a post-traumatic stress reactions.

Results. The main risk factors for stress symptoms in the Bosnia group were – lower rank, being deployed early in the campaign, having more deployment-related exposures, and serving on staff duties. There was no protective effect of previous deployments to the Falklands or Northern Ireland, and time off following deployment was not protective. For GHQ-12 cases, the main risk factors were: female gender, lower rank, increased deployment-related exposures and serving on staff duties.

Conclusions. This study suggests that stress symptoms and GHQ-12 cases, are strongly predicted both by experiences during deployment and demographic factors.
Impaired distractor inhibition in patients with schizophrenia on a negative priming task
Authors: MACQUEEN G. M. , GALWAY T. , GOLDBERG J. O. , TIPPER S. P.
Published: February 2003

Background. Numerous studies have suggested, via the interpretation of negative priming effects, that subjects with schizophrenia are less able than controls to inhibit irrelevant distracting information. Further issues concerning impairment in inhibitory processes are investigated here. First, recent research has revealed that negative priming (NP) effects can be caused by different processes, distractor inhibition or perceptual review. Therefore, conclusions concerning reduced inhibition in patients with schizophrenia are not possible from previous NP research. Secondly, previous NP studies have required subjects to identify some feature of the target. This is the first study to examine NP that uses a spatial task in patients with schizophrenia.

Method. Twenty-eight subjects with schizophrenia and 28 age and sex matched non-psychiatric control subjects completed a computerized NP task that eliminated the possible contribution of perceptual review.

Results. Subjects with schizophrenia had reduced levels of NP compared to control subjects on this spatial NP task (t=2·46, P<0·02). Current age, positive, negative or total PANNS scores did not correlate with negative priming scores, but post hoc analyses revealed that clozapine-treated patients had significantly greater levels of negative priming than patients receiving typical antipsychotic medications.

Conclusions. The present experiment eliminated the contribution of perceptual review to negative priming and demonstrated that when a pure measure of inhibition is taken on a localization task, patients with schizophrenia were less able to inhibit irrelevant distracting stimuli. The fact that NP was reduced in a spatial task suggested a more diffuse reduction in inhibition than previous studies that examined only identification-based responses.
Focal brain stimulation with repetitive transcranial magnetic stimulation (rTMS): implications for the neural circuitry of depression
Authors: LISANBY SARAH H.
Published: February 2003

BRAIN STIMULATION IN THE TREATMENT OF MAJOR DEPRESSION

Repetitive transcranial magnetic stimulation (rTMS) is an experimental medical procedure that is currently under investigation for its potential therapeutic value in major depression and other psychiatric and neurological disorders (Wassermann & Lisanby, 2001). The idea of using brain stimulation to treat depression dates back to the origins of ECT, and includes more recently developed techniques such as deep brain stimulation and vagus nerve stimulation. The value of brain stimulation in psychiatry is still most clearly seen in the, as yet, unparalleled efficacy of ECT in treating severe depression (American Psychiatric Association, 2001). While ECT is the most effective and most rapidly acting treatment for depression, it also causes a variable degree of undesirable cognitive side effects that limit its clinical utility and prevent many patients who could benefit from receiving this often life-saving treatment (McElhiney et al. 1995; Lisanby et al. 2000b). The search for an effective somatic treatment for medication resistant depression with fewer cognitive side effects than ECT has motivated much of the work with rTMS in psychiatry.
The link between cannabis use and psychosis: furthering the debate
Authors: DEGENHARDT LOUISA
Published: February 2003

The issue of whether an association exists between cannabis and psychosis exists, and why, has received considerable attention in recent years (Hall, 1998; Mueser et al. 1998; Blanchard et al. 2000; Degenhardt & Hall, 2002). There are probably a number of reasons for the sustained interest. First, psychotic disorders such as schizophrenia are often chronic or recurring (Mason et al. 1996), are associated with significant disability (Keith et al. 1991) and they place a considerable burden upon the community at large (Hall et al. 1985; Knapp, 1997). Secondly, over the past few decades, high rates of cannabis use and use disorders have been observed among persons with schizophrenia and other psychoses (Barbee et al. 1989; Fowler et al. 1998), suggesting the possibility that cannabis use may be causally related to psychotic disorders. Thirdly, given what is known about the psychotomimetic effects of cannabis (Hall et al. 2001), it is plausible that high doses of cannabis may produce psychotic symptoms. Finally, clinical research with persons with psychotic disorders has found that problematical substance use is correlated with a range of negative outcomes including relapse, rehospitalization, poor medication compliance, poorer social functioning and increased treatment costs (Salyers & Mueser, 2001), suggesting drug use may be related to worsened clinical outcomes.
Opportunistic Mycobacterial Granuloma in a Cat Associated with a Member of the Mycobacterium Terrae Complex
Authors: Henderson SM , Baker J , Williams R , Gunn-Moore DA
Published: February 2003

An 18-month-old domestic short-haired neutered male cat presented with a nodular dermal thickening on a digit. Biopsy demonstrated pyogranulomatous inflammation with moderately frequent acid-fast bacilli. A member of the Mycobacterium terrae complex was isolated. There was no evidence of systemic involvement. Treatment was initiated with enrofloxacin, rifampicin and clarithromycin. After 2 months there was no longer any clinically apparent dermal thickening. Treatment was continued for a further 3 months using enrofloxacin and rifampicin.
Triiodothyronine enhances the regenerative capacity of the liver following partial hepatectomy
Authors: Malik Raza , Mellor Neil , Selden Clare , Hodgson Humphrey
Published: February 2003

This study investigates the effects of administering a primary mitogen, triiodothyronine (T3), at the time of 70% partial hepatectomy (PH) in the rat, thus combining the 2 distinct pathways of liver growth: direct hyperplasia and compensatory regeneration. T3enhances the proliferative response of hepatocytes within the liver following PH. Flash bromodeoxyuridine (BrdU) labeling showed a cell proliferation index 24 hours after PH alone of 26.5% ± 2.8%; when T3was administered at PH, it increased to 39.5% ± 5.0% (P< .01 compared with PH alone). Continuous BrdU labeling performed every 6 hours between 15 and 72 hours following surgery showed an index of 84.0% ± 4.0% when T3was administered at PH compared with 71.0% ± 4.0% with PH alone (P< .01 compared with PH alone). This increase in cell proliferation resulted in a larger liver mass at 4 days in rats receiving T3at PH compared with PH alone (P< .05 compared with PH alone). The difference in liver mass was matched with corresponding increases in total DNA and total protein levels as well as cell division, as confirmed by the frequent demonstration of twin daughter cells on histology. In conclusion, this study shows that a single dose of T3enhances the regenerative capacity of the liver following PH. The ability to enhance cell proliferation during compensatory hyperplasia following PH could be therapeutically valuable if applicable to humans.
Cyclooxygenase-derived products modulate the increased intrahepatic resistance of cirrhotic rat livers
Authors: Graupera Mariona , García-Pagán Joan-Carles , Abraldes Juan G. , Peralta Carmen , Bragulat Mireia , Corominola Helena , Bosch Jaume , Rodés Juan
Published: February 2003

In cirrhotic livers, increased resistance to portal flow, in part due to an exaggerated response to vasoconstrictors, is the primary factor in the pathophysiology of portal hypertension. Our aim was to evaluate the response of the intrahepatic circulation of cirrhotic rat livers to the α1-adrenergic vasoconstrictor methoxamine and the mechanisms involved in its regulation. A portal perfusion pressure dose-response curve to methoxamine was performed in control and cirrhotic rat livers preincubated with vehicle, the nitric oxide synthase blocker NG
-nitro-l-arginine (l-NNA), indomethacin cyclooxygenase (COX) inhibitor, l-NNA + indomethacin, or the thromboxane (TX) A2 receptor blocker SQ 29,548. TXA2 production, COX-1 and COX-2 mRNA expression, and immunostaining for TXA2 synthase were evaluated. Cirrhotic livers exhibited a hyperresponse to methoxamine associated with overexpression of COX-2 and TXA2 synthase as well as with increased production of TXA2. The hyperresponse to methoxamine of cirrhotic livers disappeared by COX inhibition with indomethacin but not after NO inhibition. SQ 29,548 also corrected the hyperresponse of cirrhotic livers to methoxamine. In conclusion, COX-derived prostanoids, mainly TXA2, play a major role in regulating the response of cirrhotic livers to methoxamine.
Foxf1 +/− mice exhibit defective stellate cell activation and abnormal liver regeneration following CCl4 injury
Authors: Kalinichenko Vladimir V. , Bhattacharyya Dibyendu , Zhou Yan , Gusarova Galina A. , Kim Wooram , Shin Brian , Costa Robert H.
Published: February 2003

Previous studies have shown that haploinsufficiency of the splanchnic and septum transversum mesoderm Forkhead Box (Fox) f1 transcriptional factor caused defects in lung and gallbladder development and that Foxf1 heterozygous (+/−) mice exhibited defective lung repair in response to injury. In this study, we show that Foxf1 is expressed in hepatic stellate cells in developing and adult liver, suggesting that a subset of stellate cells originates from septum transversum mesenchyme during mouse embryonic development. Because liver regeneration requires a transient differentiation of stellate cells into myofibroblasts, which secrete type I collagen into the extracellular matrix, we examined Foxf1 +/− liver repair following carbon tetrachloride injury, a known model for stellate cell activation. We found that regenerating Foxf1 +/− liver exhibited defective stellate cell activation following CCl4 liver injury, which was associated with diminished induction of type I collagen, α-smooth muscle actin, and Notch-2 protein and resulted in severe hepatic apoptosis despite normal cellular proliferation rates. Furthermore, regenerating Foxf1 +/− livers exhibited decreased levels of interferon-inducible protein 10 (IP-10), delayed induction of monocyte chemoattractant protein 1 (MCP-1) levels, and aberrantly elevated expression of transforming growth factor β1. In conclusion, Foxf1 +/− mice exhibited abnormal liver repair, diminished activation of hepatic stellate cells, and increased pericentral hepatic apoptosis following CCl4 injury.
Characterization of cell types during rat liver development
Authors: Fiegel Henning C. , Park Jonas J. H. , Lioznov Michael V. , Martin Andreas , Jaeschke-Melli Stefan , Kaufmann Peter M. , Fehse Boris , Zander Axel R. , Kluth Dietrich
Published: February 2003

Hepatic stem cells have been identified in adult liver. Recently, the origin of hepatic progenitors and hepatocytes from bone marrow was demonstrated. Hematopoietic and hepatic stem cells share the markers CD 34, c-kit, and Thy1. Little is known about liver stem cells during liver development. In this study, we investigated the potential stem cell marker Thy1 and hepatocytic marker CK-18 during liver development to identify putative fetal liver stem cell candidates. Livers were harvested from embryonic and fetal day (ED) 16, ED 18, ED 20, and neonatal ED 22 stage rat fetuses from Sprague-Dawley rats. Fetal livers were digested by collagenase-DNAse solution and purified by percoll centrifugation. Magnetic cell sorting (MACS) depletion of fetal liver cells was performed using OX43 and OX44 antibodies. Cells were characterized by immunocytochemistry for Thy1, CK-18, and proliferating cell antigen Ki-67 and double labeling for Thy1 and CK-18. Thy1 expression was found at all stages of liver development before and after MACS in immunocytochemistry. Thy1 positive cells were enriched after MACS only in early developmental stages. An enrichment of CK-18 positive cells was found after MACS at all developmental stages. Cells coexpressing Thy1 and CK-18 were identified by double labeling of fetal liver cell isolates. In conclusion, hepatic progenitor cells (CK-18 positive) in fetal rat liver express Thy1. Other progenitors express only CK-18. This indicates the coexistence of different hepatic cell compartments. Isolation and further characterization of such cells is needed to demonstrate their biologic properties.
Dominant negative MORT1/FADD rescues mice from CD95 and TNF-induced liver failure
Authors: Schuchmann Marcus , Varfolomeev Eugene E. , Hermann Frank , Rueckert Felix , Strand Dennis , Koehler Heinz , Strand Susanne , Lohse Ansgar W. , Wallach David , Galle Peter R.
Published: February 2003

Derangement of the apoptotic program is considered an important cause of liver disease. It became clear that receptor-mediated apoptosis is of specific interest in this context, and CD95 and CD120a, both members of the tumor necrosis factor (TNF) receptor superfamily, are the most prominent cell death receptors involved. The death signal is induced upon ligand binding by recruitment of caspases via the adapter molecule MORT1/FADD to the receptor and their subsequent activation. To investigate the role of MORT1/FADD in hepatocyte apoptosis, we generated transgenic mice expressing liver-specific dominant negative mutant. Mice looked grossly normal; breeding and liver development were not different compared with wild-type littermates. Expression of the transgene completely protected animals from liver failure induced by the anti-Fas antibody Jo2, whereas control animals died as expected 3 to 6 hours after i.p. injection of 15 μg antibody from acute hemorrhagic liver failure. Histology demonstrated only moderate inflammatory changes in the transgenic animals, whereas severe hemorrhagic hepatitis was observed in controls. Similar results were obtained in a model of TNF-mediated liver failure, in which transgenic animals survived significantly better than wild-type animals. In conclusion, our experiments provide evidence that MORT1/FADD is indispensable for Fas and TNF-mediated hepatic injury. This is not only of great importance for targeting future therapies for liver disease but might also serve as an intriguing model to study other causes of liver injury.
Spontaneous viral clearance in patients with acute hepatitis C can be predicted by repeated measurements of serum viral load
Authors: Hofer Harald , Watkins-Riedel Thomas , Janata Oskar , Penner Edward , Holzmann Heidemarie , Steindl-Munda Petra , Gangl Alfred , Ferenci Peter
Published: February 2003

Early interferon (IFN) therapy prevents viral persistence in acute hepatitis C, but in view of the resulting costs and morbidity patients who really need therapy have to be identified. Twelve consecutive patients with acute hepatitis C (9 women, 3 men, mean age: 39.5 ± 18.8 y, genotype 1: 7, genotype 3a: 3, 2 could not be genotyped) were studied. The sources of infection were medical procedures in 6, sexual transmission in 3, and intravenous drug abuse in 3 patients. Viral load was measured by Cobas Amplicor HCV Monitor v2.0 (Roche Diagnostic Systems, Branchburg, NY). The time from infection to clinical symptoms was 43.3 ± 8.6 (mean ± SD) days. Eight patients cleared hepatitis C virus (HCV) spontaneously and remained HCV-RNA negative with a follow-up of 9.0 ± 3.9 months. In these patients viral load declined fast and continuously. The time from exposure to HCV-RNA negativity was 77.4 ± 25.3 and from the first symptoms was 34.7 ± 22.1 days. In 4 patients HCV-RNA levels remained high or even increased. Two of them became sustained responders to treatment initiated after a 6-week observation period. The 2 remaining patients were not treated (one because of contraindications for IFN, the other declined therapy) and are still HCV-RNA positive. In conclusion, patients with acute icteric hepatitis C have a high rate of spontaneous viral clearance within the first month after the onset of symptoms. IFN therapy appears only needed in patients who fail to clear the virus within 35 days after onset of symptoms. By this approach, IFN therapy was not necessary in two thirds of patients with acute hepatitis C.
A vasopressin receptor antagonist (VPA-985) improves serum sodium concentration in patients with hyponatremia: A multicenter, randomized, placebo-controlled trial
Authors: Wong Florence , Blei Andres T. , Blendis Laurence M. , Thuluvath Paul J.
Published: February 2003

Hyponatremia in advanced cirrhosis and ascites or congestive heart failure (CHF) is the result of an inappropriate increase in vasopressin secretion, which acts through activation of specific V2 receptors in the distal renal nephron to increase water reabsorption. This study investigates the efficacy and safety of 3 different doses of the V2 receptor antagonist, VPA-985, in correcting hyponatremia over a 7-day inpatient study period. Forty-four hospitalized patients (33 patients with cirrhosis, 6 with CHF, and 5 with syndrome of inappropriate antidiuretic hormone (SIADH) were studied on a constant sodium intake, with VPA doses of 25, 125, and 250 mg twice daily or placebo. Serum sodium measurements were repeated after every daily dose, and the next dose withheld for excessive serum sodium rises. Fluid intake was adjusted according to previous 24-hour urinary outputs. Adverse events were based on clinical signs of dehydration or encephalopathy. VPA-985 produced a significant overall aquaretic response compared with placebo, with significant dose related increases in free water clearance (P < .05) and serum sodium (P < .05), without significant changes in orthostatic blood pressure or serum creatinine levels. Five patients (50%) on 250 mg twice daily had to have medication withheld on multiple occasions. End-of-study plasma vasopressin levels increased significantly in the 2 larger dose groups. In conclusion, VPA-985 appears effective and safe in appropriate doses in correcting abnormal renal water handling and hyponatremia in conditions associated with water retention. Higher doses of VPA-985 may produce significant dehydration and will require close monitoring with their use.
Expression profiling in multistage hepatocarcinogenesis: Identification of HSP70 as a molecular marker of early hepatocellular carcinoma
Authors: Chuma Makoto , Sakamoto Michiie , Yamazaki Ken , Ohta Tsutomu , Ohki Misao , Asaka Masahiro , Hirohashi Setsuo
Published: February 2003

Hepatocellular carcinoma (HCC) associated with chronic liver disease evolves from precancerous lesions and early HCC to a progressed form. Nodule-in-nodule-type HCC (progressed HCC within early HCC) represents the transition from early to progressed HCC and, therefore, is useful in molecular genetic analysis of HCC progression during multistage carcinogenesis. We compared expression profiles among 7 early components and 7 progressed components of nodule-in-nodule-type HCCs and their corresponding noncancerous liver tissues with oligonucleotide array. Of the approximately 12,600 genes that were analyzed, a set of 95 genes provided a molecular signature that distinguished between early HCC components and their noncancerous liver tissues, and a set of 92 genes distinguished between progressed and early HCC components. Of these genes, the most abundantly up-regulated gene in early HCC components (P < .001) was heat-shock protein 70 (HSP70). Real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) confirmed this finding. Further immunohistochemical examination of HSP70 revealed its significant overexpression in early HCC compared with precancerous lesions (P < .001) and in progressed HCC compared with early HCC (P < .001). In conclusion, molecular signatures were clearly different in noncancerous liver tissue as compared with the early and progressed components of nodule-in-nodule-type HCC. Moreover, HSP70 could be a sensitive marker for the differential diagnosis of early HCC from precancerous lesion or noncancerous liver, a difficult distinction for pathologists due to very well differentiated histology with little atypia in early HCC.
Adherence and mental side effects during hepatitis C treatment with interferon alfa and ribavirin in psychiatric risk groups
Authors: Schaefer Martin , Schmidt Folkhard , Folwaczny Christian , Lorenz Reinhard , Martin Gaby , Schindlbeck Norbert , Heldwein Walter , Soyka Michael , Grunze Heinz , Koenig August , Loeschke Klaus
Published: February 2003

Psychiatric disorders or drug addiction are often regarded as contraindications against the use of interferon alfa (IFN-α) in patients with chronic hepatitis C. Our aim was to obtain prospective data on adherence to as well as efficacy and mental side effects of treatment with IFN-α in different psychiatric risk groups compared with controls. In a prospective trial, 81 patients with chronic hepatitis C (positive hepatitis C virus[HCV] RNA and elevated alanine aminotransferase[ALT] level) and psychiatric disorders (n = 16), methadone substitution (n = 21), former drug addiction (n = 21), or controls without a psychiatric history or drug addiction (n = 23) were treated with a combination of IFN-α-2a 3 MU 3 times weekly and ribavirin (1,000-1,200 mg/d). Sustained virologic response (overall, 37%) did not differ significantly between subgroups. No significant differences between groups were detected with respect to IFN-α-related development of depressions during treatment. However, in the psychiatric group, significantly more patients received antidepressants before and during treatment with IFN-α (P < .001). Most of those who dropped out of the study were patients with former drug addiction (43%; P = .04) compared with 14% in the methadone group, 13% in the control group, and 18% in the psychiatric group. No patient in the psychiatric group had to discontinue treatment because of psychiatric deterioration. In conclusion, our data do not confirm the supposed increased risk for IFN-α-induced mental side effects and dropouts in psychiatric patients if interdisciplinary care and antidepressant treatment are available. Preexisting psychiatric disorders or present methadone substitution should no longer be regarded as contraindications to treatment of chronic hepatitis C with IFN-α and ribavirin in an interdisciplinary setting.
Nadolol plus spironolactone in the prophylaxis of first variceal bleed in nonascitic cirrhotic patients: A preliminary study
Authors: Abecasis Raquel , Kravetz David , Fassio Eduardo , Ameigeiras Beatriz , Garcia Daniel , Isla Rogelio , Landeira Graciela , Dominguez Nora , Romero Gustavo , Argonz Julio , Terg Ruben
Published: February 2003

Treatment with β-blockers fails to decrease portal pressure in nearly 40% of cirrhotic patients. Recent studies have suggested that treatment with spironolactone reduces pressure and flow in the portal and variceal systems. This trial was designed to assess if nadolol plus spironolactone is more effective than nadolol alone to prevent the first variceal bleeding. One hundred patients with medium and large varices who had never bled and were without ascites were included in a prospective, randomized, multicenter, double-blind, placebo-controlled trial. The patients were randomized into 2 groups: 51 received nadolol plus placebo (N + P) and 49 received nadolol plus spironolactone 100 mg/d (N + S). Hepatic venous pressure gradient (HVPG) and activity of the renin-aldosterone system (plasma renin activity/plasma aldosterone levels) were measured in 24 patients. There were no significant differences in the appearance of variceal bleeding and ascites between groups at a mean follow-up of 22 ± 16 months. However, analyzing both complications together, the incidence was significantly higher in the N + P group than in the N + S group (39% vs. 20%; P < .04). Clinical ascites was also higher in patients in the N + P group than in the N + S group (21% vs. 6%; P < .04). Significant increases in plasma renin activity and plasma aldosterone levels were only observed in patients in the N + S group (P < .01). The cumulative probabilities of remaining free of bleeding and ascites were similar in both groups after 70 months of follow-up. In conclusion, these results suggest that nadolol plus spironolactone does not increase the efficacy of nadolol alone in the prophylaxis of the first variceal bleeding. However, when bleeding and ascites were considered together, the combined therapy effectively reduced the incidence of both portal-hypertensive complications.