bluuebunny/crossref_metadata_2025_split huggingface dataset:
Position paper on diagnosis and treatment of atopic dermatitis
Authors: Darsow U , Lübbe J , Taïeb A , Seidenari S , Wollenberg A , Calza AM , Giusti F , Ring J ,   for the European Task Force on Atopic Dermatitis
Published: April 2005

ABSTRACTThe diagnosis of atopic dermatitis (AD) is made using evaluated clinical criteria. Management of AD must consider the symptomatic variability of the disease. It is based on hydrating topical treatment, and avoidance of specific and unspecific provocation factors. Anti‐inflammatory treatment is used for exacerbation management. Topical corticosteroids remain the first choice. Systemic anti‐inflammatory treatment should be kept to a minimum, but may be necessary in rare refractory cases. The new topical calcineurin inhibitors (tacrolimus and pimecrolimus) expand the available choices of topical anti‐inflammatory treatment. Microbial colonization and superinfection (e.g. with Staphylococcus aureus, Malassezia furfur) can have a role in disease exacerbation and can justify the use of antimicrobials in addition to the anti‐inflammatory treatment. Evidence for the efficacy of systemic antihistamines in relieving pruritus is still insufficient, but some patients seem to benefit. Adjuvant therapy includes ultraviolet (UV) irradiation preferably of UVA wavelength; UVB 311 nm has also been used successfully. Dietary recommendations should be specific and only given in diagnosed individual food allergy. Stress‐induced exacerbations may make psychosomatic counselling recommendable. ‘Eczema school’ educational programmes have proved to be helpful.
Functional analysis of the foot and ankle myology of gibbons and bonobos
Authors: Vereecke Evie E. , D’Août Kristiaan , Payne Rachel , Aerts Peter 
Published: April 2005

AbstractThis study investigates the foot and ankle myology of gibbons and bonobos, and compares it with the human foot. Gibbons and bonobos are both highly arboreal species, yet they have a different locomotor behaviour. Gibbon locomotion is almost exclusively arboreal and is characterized by speed and mobility, whereas bonobo locomotion entails some terrestrial knuckle‐walking and both mobility and stability are important. We examine if these differences in locomotion are reflected in their foot myology. Therefore, we have executed detailed dissections of the lower hind limb of two bonobo and three gibbon cadavers. We took several measurements on the isolated muscles (mass, length, physiological cross sectional area, etc.) and calculated the relative muscle masses and belly lengths of the major muscle groups to make interspecific comparisons. An extensive description of all foot and ankle muscles is given and differences between gibbons, bonobos and humans are discussed. No major differences were found between the foot and ankle musculature of both apes; however, marked differences were found between the ape and human foot. The human foot is specialized for solely one type of locomotion, whereas ape feet are extremely adaptable to a wide variety of locomotor modes. Apart from providing interesting anatomical data, this study can also be helpful for the interpretation of fossil (pre)hominids.
Increased oxidative damage in nuclear and mitochondrial DNA in Alzheimer's disease
Authors: Wang J. , Xiong S. , Xie C. , Markesbery W. R. , Lovell M. A. 
Published: April 2005

AbstractIncreasing evidence suggests that oxidative stress is associated with normal aging and several neurodegenerative diseases, including Alzheimer's disease (AD). Here we quantified multiple oxidized bases in nuclear and mitochondrial DNA of frontal, parietal, and temporal lobes and cerebellum from short postmortem interval AD brain and age‐matched control subjects using gas chromatography/mass spectrometry with selective ion monitoring (GC/MS‐SIM) and stable labeled internal standards. Nuclear and mitochondrial DNA were extracted from eight AD and eight age‐matched control subjects. We found that levels of multiple oxidized bases in AD brain specimens were significantly (p < 0.05) higher in frontal, parietal, and temporal lobes compared to control subjects and that mitochondrial DNA had approximately 10‐fold higher levels of oxidized bases than nuclear DNA. These data are consistent with higher levels of oxidative stress in mitochondria. Eight‐hydroxyguanine, a widely studied biomarker of DNA damage, was approximately 10‐fold higher than other oxidized base adducts in both AD and control subjects. DNA from temporal lobe showed the most oxidative damage, whereas cerebellum was only slightly affected in AD brains. These results suggest that oxidative damage to mitochondrial DNA may contribute to the neurodegeneration of AD.
Elevation of the Hsp70 chaperone does not effect toxicity in mouse models of familial amyotrophic lateral sclerosis
Authors: Liu Jian , Shinobu Leslie A. , Ward Christopher M. , Young Darren , Cleveland Don W. 
Published: April 2005

AbstractMutations in copper/zinc superoxide dismutase (SOD1) account for 10–20% of a familial form of amyotrophic lateral sclerosis (ALS). A common feature of SOD1 mutants is abnormal aggregation of the aberrant SOD1 in neurons and glia. We now report that in ALS transgenic mouse models the constitutively expressed heat shock protein 70 (Hsp70) is mislocalized into aggregates together with mutant SOD1 and ubiquitin. Forcing increased synthesis of Hsp70 ameliorates both aggregate formation and toxicity in primary motor neurons in culture. However, chronic increase in an inducible form of Hsp70 to about 10‐fold its normal level is shown here not to affect disease course or pathology developed in mice from accumulation of any of three familial ALS causing SOD1 mutants with different underlying biochemical characteristics. Therefore, increasing Hsp70 to a level that is protective in mouse models of acute ischemic insult and selected neurodegenerative disorders is not sufficient to ameliorate mutant SOD1‐mediated toxicity.
Modulatory effects of progesterone on inducible nitric oxide synthase expression in vivo and in vitro
Authors: Coughlan Teresa , Gibson Claire , Murphy Sean 
Published: April 2005

AbstractNitric oxide (NO) is produced in the CNS following injury‐induced expression of inducible nitric oxide synthase (iNOS), yet its role as protective or damaging is unclear. Previous studies investigating the therapeutic potential of female sex steroids in stroke and trauma suggest that NO from this source is harmful, since oestradiol and progesterone decreased the level of iNOS expression in vitro and improved neurological outcome. We investigated the effects of progesterone on stroke‐induced expression of iNOS in mice, as well as cytokine‐induced expression of iNOS and its transcriptional activators in cells relevant to injury. We observed a significant reduction in stroke‐induced iNOS transcript in progesterone‐treated mice and in cultured macrophages. In contrast, progesterone significantly amplifed cytokine‐induced iNOS mRNA in cultured primary astrocytes, although the expression of protein was decreased. We sequenced upstream of the 1.5 kb reported iNOS promoter region and identified a potential progesterone response element (PRE). Astrocytes transiently transfected with iNOS promoter/CAT reporter gene constructs containing the PRE displayed a significant increase in induction of CAT expression after progesterone treatment, and this was diminished in cells transfected with a construct containing a disrupted PRE. These observations suggest the involvement of iNOS in the neuroprotective effects of progesterone.
In vivo up‐regulation of brain‐derived neurotrophic factor in specific brain areas by chronic exposure to Δ9‐tetrahydrocannabinol
Authors: Butovsky Elena , Juknat Ana , Goncharov Igor , Elbaz Judith , Eilam Raya , Zangen Abraham , Vogel Zvi 
Published: April 2005

AbstractCannabinoids are widely abused drugs. Here we show that chronic administration of Δ9‐tetrahydrocannabinol (Δ9‐THC), the active psychotropic agent in marijuana and hashish, at 1.5 mg per kg per day intraperitoneally for 7 days, increases the expression, at both mRNA and protein levels, of brain‐derived neurotrophic factor (BDNF), in specific rat brain areas, notably in those involved in reward and addiction. Real‐time PCR revealed a 10‐fold up‐regulation of BDNF mRNA in the nucleus accumbens (NAc) upon chronic Δ9‐THC treatment, but there was no change at 3 or 24 h after a single injection. Smaller increases in mRNA levels were found in the ventral tegmental area (VTA), medial prefrontal cortex and paraventricular nucleus (PVN). Immunohistochemistry showed large increases in BDNF‐stained cells in the NAc (5.5‐fold), posterior VTA (4‐fold) and PVN (1.7‐fold), but no change was observed in the anterior VTA, hippocampus or dorsal striatum. Altogether, our study indicates that chronic exposure to Δ9‐THC up‐regulates BDNF in specific brain areas involved with reward, and provides evidence for different BDNF expression in the anterior and posterior VTA. Moreover, BDNF is known to modulate synaptic plasticity and adaptive processes underlying learning and memory, leading to long‐term functional and structural modification of synaptic connections. We suggest that Δ9‐THC up‐regulation of BDNF expression has an important role in inducing the neuroadaptive processes taking place upon exposure to cannabinoids.
Suberoylanilide hydroxamic acid (SAHA) has potent anti‐glioma properties in vitro, ex vivo and in vivo
Authors: Eyüpoglu Ilker Y. , Hahnen Eric , Buslei Rolf , Siebzehnrübl Florian A. , Savaskan Nicolai E. , Lüders Mike , Tränkle Christian , Wick Wolfgang , Weller Michael , Fahlbusch Rudolf , Blümcke Ingmar 
Published: April 2005

AbstractCurrent treatment modalities for malignant gliomas do not allow long‐term survival. Here, we identify suberoylanilide hydroxamic acid (SAHA), an inhibitor of histone deacetylases (HDAC), as an effective experimental anti‐glioma agent. Administration of SAHA to various glioma cell lines obtained from human, rat and mouse inhibited tumour cell growth in a range of 1–10 μm. This anti‐glioma property is associated with up‐regulation of the cell cycle control protein p21/WAF, as well as the induction of apoptosis. A novel tumour invasion model using slice cultures of rat brain corroborated the anti‐glioma properties of SAHA in the organotypic brain environment. In this model, glioma invasion compromised adjacent brain parenchyma, and this tumour‐associated cytotoxicity could be inhibited by SAHA. In addition, a 10‐fold dose escalation experiment did not challenge the viability of cultured brain slices. In vivo, a single intratumoural injection of SAHA 7 days after orthotopic implantation of glioma cells in syngeneic rats doubled their survival time. These observations identify chromatin‐modifying enzymes as possible and promising targets for the pharmacotherapy of malignant gliomas.
Sm–Nd and U–Pb dating of high‐pressure granulites from the Złote and Rychleby Mts (Bohemian Massif, Poland and Czech Republic)
Authors: LANGE U. , BRÖCKER M. , ARMSTRONG R. , TRAPP E. , MEZGER K. 
Published: April 2005

AbstractIn the Orlica‐Śnieżnik complex at the NE margin of the Bohemian Massif, high‐pressure granulites occur as isolated lenses within partially migmatized orthogneisses. Sm–Nd (different grain‐size fractions of garnet, clinopyroxene and/or whole rock) and U–Pb [isotope dilution‐thermal ionization mass spectrometry (ID‐TIMS) single grain and sensitive high‐resolution ion microprobe (SHRIMP)] ages for granulites, collected in the surroundings of Červený Důl (Czech Republic) and at Stary Gierałtów (Poland), constrain the temporal evolution of these rocks during the Variscan orogeny. Most of the new ages cluster atc.350–340 Ma and are consistent with results previously reported for similar occurrences throughout the Bohemian Massif. This interval is generally interpreted to constrain the time of high‐pressure metamorphism. A more complex evolution is recorded for a mafic granulite from Stary Gierałtów and concerns the unknown duration of metamorphism (single, short‐lived metamorphic cycle or different episodes that are significantly separated in time?). The central grain parts of zircon from this sample yielded a large spread in apparent206Pb/238U SHRIMP ages (c.462–322 Ma) with a distinct cluster atc.365 Ma. This spread is interpreted to be indicative for variable Pb‐loss that affected magmatic protolith zircon during high‐grade metamorphism. The initiating mechanism and the time of Pb‐loss has yet to be resolved. A connection to high‐pressure metamorphism atc. 350–340 Ma is a reasonable explanation, but this relationship is far from straightforward. An alternative interpretation suggests that resetting is related to a high‐temperature event (not necessarily in the granulite facies and/or at high pressures) around 370–360 Ma, that has previously gone unnoticed. This study indicates that caution is warranted in interpreting U–Pb zircon data of HT rocks, because isotopic rejuvenation may lead to erroneous conclusions.
Timing and nature of fluid flow and alteration during Mesoproterozoic shear zone formation, Olary Domain, South Australia
Authors: CLARK C. , MUMM A. SCHMIDT , FAURE K. 
Published: April 2005

AbstractThe development of shear zones at mid‐crustal levels in the Proterozoic Willyama Supergroup was synchronous with widespread fluid flow resulting in albitization and calcsilicate alteration. Monazite dating of shear zone fabrics reveal that they formed at 1582 ± 22 Ma, at the end of the Olarian D3 deformational event and immediately prior to the emplacement of regional S‐type granites. Two stages of fluid flow are identified in the area: first an albitizing event which involved the addition of Na and loss of Si, K and Fe; and a second phase of calcsilicate alteration with additions of Ca, Fe, Mg and Si and removal of Na. Fluid fluxes calculated for albitization and calcsilicate alteration were 5.56 × 109 to 1.02 × 1010 mol m−2 and 2.57 × 108–5.20 × 109 mol m−2 respectively. These fluxes are consistent with estimates for fluid flow through mid‐crustal shear zones in other terranes. The fluids associated with shearing and alteration are calculated to have δ18O and δD values ranging between +8 and +11‰, and −33 and −42‰, respectively, and ɛNd values between −2.24 and −8.11. Our results indicate that fluids were derived from metamorphic dehydration of the Willyama Supergroup metasediments. Fluid generation occurred during prograde metamorphism of deeper crustal rocks at or near peak pressure conditions. Shear zones acted as conduits for major crustal fluid flow to shallow levels where peak metamorphic conditions had been attained earlier leading to the apparent ‘retrograde’ fluid‐flow event. Thus, the peak metamorphism conditions at upper and lower crustal levels were achieved at differing times, prior to regional granite formation, during the same orogenic cycle leading to the formation of retrograde mineral assemblages during shearing.
An investigation of the relationship between bulk composition, inferred reaction progress and fluid‐flow parameters for layered micaceous carbonates from Maine, USA
Authors: EVANS K. A. , BICKLE M. J. 
Published: April 2005

AbstractReaction progress exhibited by multivariant assemblages in micaceous limestones can provide an excellent record of metamorphic fluid flow. However, it is necessary to understand the sensitivity of these assemblages to bulk‐composition parameters. Here, analysis of bulk composition on different scales and pseudosection construction are used to draw conclusions on relationships between bulk composition, fluid flow and reaction progress. Issues addressed include the effects of bulk composition on the mineralogical evolution of micaceous carbonates, the sensitivity of bulk composition to bulk‐composition sampling methods, the magnitude of cross‐layer fluid‐composition gradients, the potential for metasomatism to drive reaction progress, and the relative timing of reaction in adjacent layers. Pseudosections successfully represent observed mineral assemblages, constrain the position of reactions in T–X(CO2) space, and allow assessment of the sensitivity of reaction position, inferred reaction progress and calculated fluid fluxes to uncertainties in bulk composition. The scale of bulk‐composition sampling affects bulk compositions, calculated modes, predicted mineral assemblages and calculated fluid compositions. Larger samples record an average of different lithological subdomains, while point‐count‐derived bulk compositions are subject to uncertainties related to the small number of sample points. The optimum bulk composition for pseudosection purposes probably lies between measured bulk compositions. Results suggest that reaction progress in some extensively reacted layers was driven by infiltration of H2O‐rich fluid which flowed or diffused parallel to layering, perpendicular to layering in response to fluid‐composition gradients, and out of veins. Small variations in fluid composition across layering (ΔX(CO2) < 0.02) were maintained by internal buffering by the mineral assemblages. Internal buffering must also have driven samples up a sequence of narrow low‐variance fields in T–X(CO2) space, and so reaction in adjacent layers must have close to simultaneous. Metasomatic effects on reaction progress are likely to have been small, so long as the porosity was low.
Inhibition of Persistent Sodium Current Fraction and Voltage‐gated L‐type Calcium Current by Propofol in Cortical Neurons: Implications for Its Antiepileptic Activity
Authors: Martella Giuseppina , De Persis Cristiano , Bonsi Paola , Natoli Silvia , Cuomo Dario , Bernardi Giorgio , Calabresi Paolo , Pisani Antonio 
Published: April 2005

Summary:  Purpose: Although it is widely used in clinical practice, the mechanisms of action of 2,6‐di‐isopropylphenol (propofol) are not completely understood. We examined the electrophysiologic effects of propofol on an in vitro model of epileptic activity obtained from a slice preparation. Methods: The effects of propofol were tested both on membrane properties and on epileptiform events consisting of long‐lasting, paroxysmal depolarization shifts (PDSs) induced by reducing the magnesium concentration from the solution and by adding bicuculline and 4‐aminopyridine.These results were integrated with a patch‐clamp analysis of Na+ and high‐voltage activated (HVA) calcium (Ca2+) currents from isolated cortical neurons. Results: In bicuculline, to avoid any interference by γ‐aminobutyric acid (GABA)‐A receptors, propofol (3–100 μM) did not cause significant changes in the current‐evoked, sodium (Na+)‐dependent action‐potential discharge. However, propofol reduced both the duration and the number of spikes of PDSs recorded from cortical neurons. Interestingly, relatively low concentrations of propofol [half‐maximal inhibitory concentration (IC50), 3.9 μM) consistently inhibited the “persistent” fraction of Na+ currents, whereas even high doses (≤300 μM) had negligible effects on the “fast” component of Na+ currents. HVA Ca2+ currents were significantly reduced by propofol, and the pharmacologic analysis of this effect showed that propofol selectively reduced L‐type HVA Ca2+ currents, without affecting N or P/Q‐type channels. Conclusions: These results suggest that propofol modulates neuronal excitability by selectively suppressing persistent Na+ currents and L‐type HVA Ca2+ conductances in cortical neurons. These effects might cooperate with the opening of GABA‐A–gated chloride channels, to achieve depression of cortical activity during both anesthesia and status epilepticus.
Hippocampal Sclerosis in Severe Myoclonic Epilepsy in Infancy: A Retrospective MRI Study
Authors: Siegler Zsuzsanna , Barsi Peter , Neuwirth Magdolna , Jerney Judit , Kassay Maria , Janszky Jozsef , Paraicz Eva , Hegyi Marta , Fogarasi Andras 
Published: April 2005

Summary: Purpose:Severe myoclonic epilepsy in infancy (SMEI; Dravet's syndrome) is a malignant epilepsy syndrome characterized by early prolonged febrile convulsions (PFCs) with secondary psychomotor delay and a variety of therapy‐resistant seizures. Although the initial symptoms are repeated PFCs, the MRI performed at the onset of disease shows no hippocampal structural abnormalities. We aimed to assess clinical and serial MRI data of patients with SMEI with a special attention to the temporomedial structures. To our knowledge, this is the first systematic MRI study in this disease.Methods:Clinical and MRI data of all SMEI patients treated in our hospitals between 1996 and 2004 were reviewed.Results:Twenty‐eight MRIs from 14 children (one to four images/patient) were included. Age at disease onset was between 3 and 9 months; age at initial MRI was 5 months to 13 years. Ten of 14 patients showed hippocampal sclerosis (HS) during the course of the disease (nine unilateral, one bilateral). Six of these 10 had a normal initial MRI. Age at the first verified HS was between 14 months and 13 years. Neither complex partial seizures nor anterior temporal irritative zone was recorded in these children.Conclusions:After initially normal structures, in most patients with SMEI, HS develops several months or years after the first PFC. These data support the hypothesis that PFC might be responsible for HS, but other factors and individual sensitivity should play a role in this process.
Entorhinal Cortex Involvement in Human Mesial Temporal Lobe Epilepsy: An Electrophysiologic and Volumetric Study
Authors: Bartolomei Fabrice , Khalil Mouhamad , Wendling Fabrice , Sontheimer Anna , Régis Jean , Ranjeva Jean‐Phillipe , Guye Maxime , Chauvel Patrick 
Published: April 2005

Summary:  Purpose: Several studies have demonstrated diminution in the volume of entorhinal cortex (EC) ipsilateral to the pathologic side in patients with temporal lobe epilepsy (TLE). The relation between the degree of EC atrophy and the epileptogenicity of this structure has never been directly studied. The purpose of the study was to determine whether atrophy of the EC evaluated by the quantitative magnetic resonance imaging (MRI) method is correlated with the epileptogenicity of this structure in TLE. Methods: Intracerebral recordings (SEEG method) of seizures from 11 patients with mesial TLE were analyzed. Seizures were classified according to patterns of onset: pattern 1 was the emergence of a low‐frequency, high‐amplitude rhythmic spiking followed by a tonic discharge, and pattern 2 was the emergence of a tonic discharge in the mesial structures. A nonlinear measure of SEEG signal interdependencies was used to evaluate the functional couplings occurring between hippocampus (Hip) and EC at seizure onset. MRI volumetric analysis was performed by using a T1‐weighted three‐dimensional gradient‐echo sequence in TLE patients and 12 healthy subjects. Results: Significant interactions between Hip and Ec were quantified at seizure onset. The EC was found to be the leader structure in most of the pattern 2 seizures. Volumetric measurements of EC demonstrated an atrophy in 63% of patients ipsilateral to the epileptic side. A significant correlation between the strength of EC–Hip coupling and the degree of atrophy was found. In addition, in those patients that had a normal EC volume, the EC was never the leader structure in Ec–Hip coupling. Conclusions: These results validate the potential role of volumetry to predict the epileptogenesis of the EC in patients with hippocampal sclerosis and MTLE.