bluuebunny/crossref_metadata_2025 huggingface dataset:
Cycloheximide treatment to identify components of the transitional transcriptome in PACAP‐induced PC12 cell differentiation
Authors: Ravni Aurélia , Eiden Lee E. , Vaudry Hubert , Gonzalez Bruno J. , Vaudry David
Published: June 2006

Pituitary adenylate cyclase‐activating polypeptide (PACAP) promotes neurite outgrowth, reduces proliferation and inhibits apoptosis of PC12 cells. We have partially characterized the transcriptome changes induced by PACAP after 6 h of treatment, when commitment to differentiation has occurred. Here, we have investigated the effects of a 6‐h treatment with PACAP (10−7 m) in the presence of cycloheximide (5 µm) to identify, via superinduction, components of the transitional transcriptome initially induced by PACAP and potentially participating in the regulation of late‐response genes required for differentiation. Approximately 100 new transcripts were identified in this screen, i.e. as many individual genes as make up the 6‐h PACAP differentiation transcriptome itself. Six known transcripts in this cohort were then measured at several time points between 0 and 6 h by real‐time PCR to determine whether these transcripts are induced early following PACAP treatment in the absence of cycloheximide, and therefore may be of functional importance in differentiation. Five out of the six transcripts were indeed induced by PACAP alone soon (between 30 min and 3 h) after cell treatment.β‐Cell translocation gene 2, antiproliferative (Btg2),serum/glucocorticoid‐regulated kinase (Sgk),nuclear factor for the κ chain of B‐cells(NFκB),seven in absentia homologue 2 (Siah2)andFBJ osteosarcoma related oncogene(Fos) showed a 2.5–200‐fold induction by PACAP between 15 min and 3 h, and mRNA levels returned either to baseline or near baseline after 6 h. This work provides new information concerning genes whose transient regulation early after PACAP exposure may contribute to the expression of the differentiated transcriptome in PC12 cells, and should help to elucidate the molecular mechanisms involved in the control of nerve cell survival and differentiation.
Presynaptic enzymatic neurotoxins
Authors: Rossetto Ornella , Morbiato Laura , Caccin Paola , Rigoni Michela , Montecucco Cesare
Published: June 2006

Botulinum neurotoxins produced by anaerobic bacteria of the genus Clostridium are the most toxic proteins known, with mouse LD50 values in the 1–5 ng/kg range, and are solely responsible for the pathophysiology of botulism. These metalloproteinases enter peripheral cholinergic nerve terminals and cleave proteins of the neuroexocytosis apparatus, causing a persistent, but reversible, inhibition of neurotransmitter release. They are used in the therapy of many human syndromes caused by hyperactive nerve terminals. Snake presynaptic PLA2 neurotoxins block nerve terminals by binding to the nerve membrane and catalyzing phospholipid hydrolysis with production of lysophospholipids and fatty acids. These compounds change the membrane conformation, causing enhanced fusion of synaptic vesicle via hemifusion intermediate with release of neurotransmitter and, at the same time, inhibition of vesicle fission and recycling. It is possible to envisage clinical applications of the lysophospholipid/fatty acid mixture to inhibit hyperactive superficial nerve terminals.
Calpain product of WT‐CRMP2 reduces the amount of surface NR2B NMDA receptor subunit
Authors: Bretin Sylvie , Rogemond Véronique , Marin Philippe , Maus Marion , Torrens Yvette , Honnorat Jérôme , Glowinski Jacques , Prémont Joël , Gauchy Christian
Published: June 2006

The brain is particularly vulnerable to ischaemia; however, neurons can become tolerant to ischaemic insult. This tolerance has been shown to involve activation of NMDA receptors, but its mechanisms have not yet been fully elucidated. Using a preconditioning protocol, we show that neurons surviving to a transient NMDA exposure become resistant to the glutamatergic agonist. Using a proteomic approach, we found that alterations of the protein pattern of NMDA‐resistant neurons are restricted mainly to the five collapsin response mediator proteins (CRMPs). A sustained increase in calpain activity following NMDA treatment is responsible for the production of cleaved CRMPs. Finally, we provide evidence for the involvement of the cleaved form of WT‐CRMP2 in the down‐regulation of NR2B. Our data suggests that, beside their role in neuronal morphogenesis, CRMPs may contribute to neuronal plasticity.
Calsenilin interacts with transcriptional co‐repressor C‐terminal binding protein(s)
Authors: Zaidi Nikhat F. , Kuplast Kristy G. , Washicosky Kevin J. , Kajiwara Yuji , Buxbaum Joseph D. , Wasco Wilma
Published: June 2006

Calsenilin/potassium channel‐interacting protein (KChIP)3/ downstream regulatory element sequence antagonist modulator (DREAM) is a neuronal calcium‐binding protein that has been shown to have multiple functions in the cell, including the regulation of presenilin processing, repression of transcription and modulation of A‐type potassium channels. To gain a better understanding of the precise role of calsenilin in specific cellular compartments, an interactor hunt for proteins that bind to the N‐terminal domain of calsenilin was carried out. Using a yeast two‐hybrid system and co‐immunoprecipitation studies, we have identified the transcriptional co‐repressor C‐terminal binding protein (CtBP)2 as an interactor for calsenilin and have shown that the two proteins can interact in vivo. In co‐immunoprecipitation studies, calsenilin also interacted with CtBP1, a CtBP2 homolog. Our data also showed a calsenilin‐dependent increase in c‐fos protein levels in CtBP knockout fibroblasts, suggesting that CtBP may modulate the transcriptional repression of c‐fos by calsenilin. Furthermore, the finding that histone deacetylase protein and activity were associated with the calsenilin–CtBP immunocomplex suggests a mechanism by which calsenilin–CtBP may act to repress transcription. Finally, we demonstrated that calsenilin and CtBP are present in synaptic vesicles and can interact in vivo.
The p53 family in nervous system development and disease
Authors: Jacobs W. Bradley , Kaplan David R. , Miller Freda D.
Published: June 2006

The p53 family, consisting of the tumor suppressors p53, p63 and p73, play a vital role as regulators of survival and apoptosis in the developing, adult and injured nervous system. These proteins function as key survival and apoptosis checkpoints in neurons, acting as either rheostats or sensors responsible for integrating multiple pro‐apoptotic and survival cues. A dramatic example of this checkpoint function is observed in developing sympathetic neurons, where a pro‐survival and truncated form of p73 antagonizes the apoptotic functions of p53 and p63. Thus the levels and activities of the different p53 family members may ultimately determine whether neurons either live or die during nervous system development and disease.
Kiss‐and‐run and full‐collapse fusion as modes of exo‐endocytosis in neurosecretion
Authors: Harata Nobutoshi C. , Aravanis Alexander M. , Tsien Richard W.
Published: June 2006

Neurotransmitters and hormones are released from neurosecretory cells by exocytosis (fusion) of synaptic vesicles, large dense‐core vesicles and other types of vesicles or granules. The exocytosis is terminated and followed by endocytosis (retrieval). More than fifty years of research have established full‐collapse fusion and clathrin‐mediated endocytosis as essential modes of exo‐endocytosis. Kiss‐and‐run and vesicle reuse represent alternative modes, but their prevalence and importance have yet to be elucidated, especially in neurons of the mammalian CNS. Here we examine various modes of exo‐endocytosis across a wide range of neurosecretory systems. Full‐collapse fusion and kiss‐and‐run coexist in many systems and play active roles in exocytotic events. In small nerve terminals of CNS, kiss‐and‐run has an additional role of enabling nerve terminals to conserve scarce vesicular resources and respond to high‐frequency inputs. Full‐collapse fusion and kiss‐and‐run will each contribute to maintaining cellular communication over a wide range of frequencies.
Nitric oxide, cell bioenergetics and neurodegeneration
Authors: Moncada Salvador , Bolaños Juan P.
Published: June 2006

Following stimulation of NMDA receptors, neurons transiently synthesize nitric oxide (NO) in a calcium/calmodulin‐dependent manner through the activation of neuronal NO synthase. Nitric oxide acts as a messenger, activating soluble guanylyl cyclase and participating in the transduction signalling pathways involving cyclic GMP. Nitric oxide also binds to cytochrome c oxidase, and is able to inhibit cell respiration in a process that is reversible and in competition with oxygen. This action can also lead to the release of superoxide anion from the mitochondrial respiratory chain. Here, we discuss recent evidence that this mitochondrial interaction represents a molecular switch for cell signalling pathways involved in the control of physiological functions. These include superoxide‐ or oxygen‐dependent modulation of gene transcription, calcium‐dependent cell signalling responses, changes in the mitochondrial membrane potential or AMP‐activated protein kinase‐dependent control of glycolysis. In pathophysiological conditions, such as brain ischaemia or neurological disorders, NO is formed excessively by NMDA receptor over‐activation in neurons, or by inducible NO synthase from neighbouring glia (microglial cells and astrocytes). Elevated NO concentrations can then interact with superoxide anion, generated by the mitochondria or by other mechanisms, leading to the formation of the powerful oxidant species peroxynitrite. During pathological conditions activation of the NAD+‐consuming enzyme poly(APD‐ribose) polymerase‐1 (PARP‐1) is also a likely mechanism for NO‐mediated energy failure and neurotoxicity. Activation of PARP‐1 is, however, a repair process, which in milder forms of oxidative stress protects neurons from death. Thus, whilst NO plays a physiological role in neuronal cell signalling, its over‐production may cause neuronal energy compromise leading to neurodegeneration.
Molecular mechanisms for Alzheimer's disease: implications for neuroimaging and therapeutics
Authors: Masters Colin L. , Cappai Roberto , Barnham Kevin J. , Villemagne Victor L.
Published: June 2006

Alzheimer's disease is a progressive neurodegenerative disorder characterised by the gradual onset of dementia. The pathological hallmarks of the disease are β‐amyloid (Aβ) plaques, neurofibrillary tangles, synaptic loss and reactive gliosis. The current therapeutic effort is directed towards developing drugs that reduce Aβ burden or toxicity by inhibiting secretase cleavage, Aβ aggregation, Aβ toxicity, Aβ metal interactions or by promoting Aβ clearance. A number of clinical trials are currently in progress based on these different therapeutic strategies and they should indicate which, if any, of these approaches will be efficacious. Current diagnosis of Alzheimer's disease is made by clinical, neuropsychologic and neuroimaging assessments. Routine structural neuroimaging evaluation with computed tomography and magnetic resonance imaging is based on non‐specific features such as atrophy, a late feature in the progression of the disease, hence the crucial importance of developing new approaches for early and specific recognition at the prodromal stages of Alzheimer's disease. Functional neuroimaging techniques such as functional magnetic resonance imaging, magnetic resonance spectroscopy, positron emission tomography and single photon emission computed tomography, possibly in conjunction with other related Aβ biomarkers in plasma and CSF, could prove to be valuable in the differential diagnosis of Alzheimer's disease, as well as in assessing prognosis. With the advent of new therapeutic strategies there is increasing interest in the development of magnetic resonance imaging contrast agents and positron emission tomography and single photon emission computed tomography radioligands that will permit the assessment of Aβ burdenin vivo.
The role of mitochondria in inherited neurodegenerative diseases
Authors: Kwong Jennifer Q. , Beal M. Flint , Manfredi Giovanni
Published: June 2006

In the past decade, the genetic causes underlying familial forms of many neurodegenerative disorders, such as Huntington's disease, Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, Friedreich ataxia, hereditary spastic paraplegia, dominant optic atrophy, Charcot‐Marie‐Tooth type 2A, neuropathy ataxia and retinitis pigmentosa, and Leber's hereditary optic atrophy have been elucidated. However, the common pathogenic mechanisms of neuronal death are still largely unknown. Recently, mitochondrial dysfunction has emerged as a potential ‘lowest common denominator’ linking these disorders. In this review, we discuss the body of evidence supporting the role of mitochondria in the pathogenesis of hereditary neurodegenerative diseases. We summarize the principal features of genetic diseases caused by abnormalities of mitochondrial proteins encoded by the mitochondrial or the nuclear genomes. We then address genetic diseases where mutant proteins are localized in multiple cell compartments, including mitochondria and where mitochondrial defects are likely to be directly caused by the mutant proteins. Finally, we describe examples of neurodegenerative disorders where mitochondrial dysfunction may be ‘secondary’ and probably concomitant with degenerative events in other cell organelles, but may still play an important role in the neuronal decay. Understanding the contribution of mitochondrial dysfunction to neurodegeneration and its pathophysiological basis will significantly impact our ability to develop more effective therapies for neurodegenerative diseases.
SNAP25 is a pre‐synaptic target for the depressant action of reactive oxygen species on transmitter release
Authors: Giniatullin A. R. , Darios F. , Shakirzyanova A. , Davletov B. , Giniatullin R.
Published: June 2006

Reactive oxygen species (ROS) participate in various physiological and pathological processes in the nervous system, but the specific pathways that mediate ROS signalling remain largely unknown. Using electrophysiological techniques and biochemical evaluation of isolated fusion proteins, we explored the sensitivity to standard oxidative stress of the entire synapse, the pre‐synaptic machinery and essential fusion proteins underlying transmitter exocytosis. Oxidative stress induced by H2O2 plus Fe2+ inhibited both evoked and spontaneous quantal release from frog or mouse motor nerve endings, while it left post‐synaptic sensitivity unchanged. The depressant effect of H2O2 on acetylcholine release was pertussis toxin‐insensitive, ruling out G‐protein cascades. Experiments with ionomycin, a Ca2+ ionophore, revealed that ROS directly impaired the function of releasing machinery. In line with this, SNAP25, one of three essential fusion proteins, showed a selectively high sensitivity to the oxidative signals. Several ROS scavengers enhanced evoked synaptic transmission, consistent with tonic inhibition by endogenous ROS. Our data suggest that ROS‐induced impairment of releasing machinery is mediated by SNAP25, which appears to be a pre‐synaptic ROS sensor. This mechanism of ROS signalling could have widespread implications in the nervous system and might contribute to the pathogenesis of neurodegenerative diseases.
Investigation of the mechanism for the relaxation of rat duodenum mediated via M1 muscarinic receptors
Authors: Hamrouni A. M. , Gudka N. , Broadley K. J.
Published: June 2006

1 Relaxation responses of the rat isolated duodenum to the putative M1 muscarinic receptor agonist, McN‐A‐343, were examined to determine whether the response was due to the release of known non‐adrenergic, non‐cholinergic relaxant neurotransmitters and to establish the involvement of M1 muscarinic receptors.

2 The role of ATP was examined with the P2 receptor antagonist, suramin, which at 30 μm antagonized the relaxant responses to α,β‐methylene ATP. The same dose, however, failed to inhibit the relaxation by McN‐A‐343.

3 The role of nitric oxide (NO) was examined with the NO synthase inhibitor, NG‐nitro‐l‐arginine methyl ester (l‐NAME; 100 μm), which failed to inhibit the responses to McN‐A‐343. As NO mediates relaxation of the duodenum via cGMP generation through guanylyl cyclase, whether the relaxation by McN‐A‐343 was also via cGMP was examined with the guanylyl cyclase inhibitor, 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one (ODQ). The relaxation responses to the NO donor, S‐nitroso‐N‐acetyl penicillamine, were inhibited in the presence of ODQ (3 μm), but not those by McN‐A‐343.

4 Release of γ‐aminobutyric acid (GABA) was examined with the GABAA receptor antagonist, bicuculline (10 μm), which shifted the concentration–response curves for the relaxation of the duodenum by GABA to the right. There was a similar degree of shift in the concentration–response curve for McN‐A‐343 by bicuculline indicating that release of GABA from enteric neurones of the duodenum could explain the relaxation response to McN‐A‐343.

5 To test whether the muscarinic receptors mediating the relaxation of the duodenum were of the M1 subtype, the susceptibility to the selective competitive antagonist, pirenzepine and the selective muscarinic toxin from green mamba, MT7, was examined. Pirenzepine (1 μm) shifted the concentration–response for McN‐A‐343 to the right in a parallel fashion with a dose ratio of 33.3 ± 20.2. This yielded a pA2 value of 7.5, which concords with those for other responses reputed to be mediated via M1 muscarinic receptors. The toxin MT7 was used as an irreversible antagonist and following incubation with the duodenum was washed from the bath. An incubation time of 30 min with 100 nm of MT7 caused a significant parallel shift in the concentration–response to McN‐A‐343 confirming the involvement of M1 muscarinic receptors.

6 This study has confirmed that McN‐A‐343 relaxes the rat duodenum via muscarinic receptors of the M1 subtype and that these receptors are probably located on enteric neurones from which their stimulation releases GABA.
Lung function after acute and repeated exposures to extremely cold air (−110°C) during whole‐body cryotherapy
Authors: Smolander J. , Westerlund T. , Uusitalo A. , Dugué B. , Oksa J. , Mikkelsson M.
Published: June 2006

Whole‐body cryotherapy (WBC) is one mode of cold therapy, during which rheumatic patients are exposed to very cold air (−110°C) in minimal clothing. It is also proposed to have a bronchodilatory effect. The aim was to examine the effects of WBC on lung function in healthy humans after acute and repeated exposures. Twenty‐five healthy, non‐smoking subjects participated in the study. They were exposed to WBC for 2 min three times per week for 12 weeks. The peak expiratory flow rate (PEF) and forced expiratory volume in 1 s (FEV1) were measured before and after (at 2 and 30 min) the first WBC, and then similarly at 4, 8 and 12 weeks. At all time points, after 30 min of the WBC the PEF values were slightly lower compared with values before the WBC, and the reductions reached statistical significance at 1 month (5·1 ± 1·2%), and at 3 months (3·2 ± 1·7%). After 30 min of the first WBC, the FEV1 was significantly reduced by 2·3 ± 0·8%, but no other changes were observed during the study. In conclusion, the WBC induced minor bronchoconstriction in healthy humans instead of proposed bronchodilatation. The WBC seems not to be harmful for lung function, but should be used with caution in susceptible individuals.
Further insights into the role of angiotensin II in kidney development
Authors: Lasaitiene Daina , Chen Yun , Adams Michael A. , Friberg Peter
Published: June 2006

Over the past decade, compelling studies have highlighted the fundamental role of the renin–angiotensin system (RAS) in renal development and long‐term control of renal function and arterial pressure. The present review provides an update of the understanding of how the RAS controls nephrogenesis and nephrovascular development. In addition, the investigations linking the perinatal development of RAS inhibition‐induced renal dysmorphology and establishment of adult blood pressure are discussed.
Physiological range of peak cardiac power output in healthy adults
Authors: Bromley Paul D. , Hodges Lynette D. , Brodie David A.
Published: June 2006

Aims  The purpose of this study was to indicate the normal range for peak cardiac power output (CPOpeak) in healthy adults and to explore age‐ and sex‐related variations of this parameter.

Methods and results  Using the non‐invasive exponential CO2 rebreathing technique [J.G. Defares, J Appl Physiol13 (1958) 159], cardiac output was measured at an exercise intensity determined to coincide with ≥95% of peak oxygen consumption in 102 healthy adults (mean ± SD, age 43 ± 13 years, body mass 74 ± 13 kg). Peak cardiac power was then computed from measurements of peak cardiac output () and peak mean arterial pressure (MAPpeak) using the equation described by Cooke et al. [Heart79 (1998) 289]. Peak oxygen consumption in the study population was 2·42 (±0·74) l min−1 and subjects achieved 101 ± 7% of this value during the measurement of . was 17·3 (±4) l min−1, and CPOpeak was computed as 4·5 (±1·2) W. CPOpeak ranged from 3·11 to 7·94 W in men and 2·53 to 5·57 W in women. Additionally, ageing appears to be associated with a significant loss of peak cardiac power in men that is not apparent in women.

Conclusion  Although the sample size remains moderate, the CPO values attained were normally distributed and these values provide a useful indication of the normal range for CPOpeak in healthy adults.
24‐h Systolic blood pressure and heart rate recordings in lean and obese adolescents
Authors: Framme Jenny , Dangardt Frida , Mårild Staffan , Osika Walter , Währborg Peter , Friberg Peter
Published: June 2006

Objective  We assessed the hypothesis that differences in day and night‐time systolic blood pressure (SBP) and heart rate (HR) recordings were smaller in obese versus lean children and adolescents, and whether measurements obtained during a school week or during weekends or holidays influenced these nocturnal falls. We also wanted to determine whether the results were influenced by gender.

Methods  Ambulatory 24‐h BP and HR measurements were performed in 80 subjects, 51 girls and 29 boys. Lean (n = 25) and obese (n = 55) subjects were classified according to body mass index (BMI)–standard deviation (SD) criteria. Forty‐eight subjects had their 24‐h recordings performed during a school week and 32 during leisure time.

Results  The SBP nocturnal dipping response was less pronounced in obese subjects (16·2 ± 6·3 mmHg) compared with lean controls (21·1 ± 5·7 mmHg) (P<0·01) of which the girls constituted most of the difference. HR change between day and night was similar in both groups being approximately 15 b/min. A small but statistical negative correlation was observed between BMI–SD and nocturnal fall in SBP (r = −0·3, P = 0·0065). In all subjects, regardless of BMI–SD, daytime SBP was higher when readings were obtained during a school week (123 ± 7 mmHg) than during weekends or holidays (119 ± 7 mmHg) (P = 0·029).

Conclusion  Obese children and adolescents showed smaller nocturnal falls in SBP compared with lean subjects. This pattern may cause increased cardiovascular loading; thus, it may reflect an early sign of high blood pressure development and adds to cardiovascular risk in young obese individuals.
The effect of lung inflation on absolute ventricular volume measurement by conductance
Authors: Haney Michael F. , Steendijk Paul , Johansson Göran , Biber Björn
Published: June 2006

Background  Conductance catheter in vivo ventricular volume measurements during lung ventilation may provide important information on left ventricular (LV) function. Breathing potentially may alter parallel conductance (Vc), complicating interpretation of the conductance‐derived volume signals. The effects of controlled positive pressure lung inflation (PPLI) on measured parallel conductance with dual‐field conductance volumetry were investigated.

Methods  Eight anaesthetized pigs were instrumented with an LV dual‐field conductance volumetry catheter. Vc was measured repeatedly, using the hypertonic saline injection method, at three different levels of lung insufflation: continuous positive airway pressure (PPLI) 0, 5, and 10 cmH2O.

Results  V
cs measured at PPLI 0, 5 and 10 cmH2O were 70·9 ± 4·8, 70·7 ± 5·5 and 70·5 ± 5·9 ml, respectively. The corresponding uncalibrated end‐diastolic volumes (EDVu) were 115·5 ± 7·1, 117·0 ± 7·5 and 117·5 ± 7·7 ml, respectively. Mean coefficients of variance for Vc and EDVu at all three PPLI levels were 3·8% and 1·25%, respectively.

Discussion  Several levels of PPLI demonstrated no systematic change in parallel conductance for LV dual‐field conductance volume signal. We concluded that lung inflation at these levels does not generate changes in Vc.
Effects of Carbamazepine and Oxcarbazepine on the Reproductive Endocrine Function in Women with Epilepsy
Authors: Löfgren Eeva , Tapanainen Juha S. , Koivunen Riitta , Pakarinen Arto , Isojärvi Jouko I. T.
Published: June 2006

Summary:  Purpose: The aim of the study was to compare the effects of carbamazepine (CBZ) and oxcarbazepine (OXC) on the reproductive endocrine function in women with epilepsy. OXC is a novel antiepileptic drug (AED), and the occurrence of reproductive dysfunction in women treated with OXC monotherapy for epilepsy has not been studied previously.

Methods: Thirty‐five women with epilepsy were examined in the Department of Neurology at Oulu University Hospital. Sixteen patients were treated with CBZ monotherapy, and nineteen patients were treated with OXC monotherapy. The subjects were clinically examined, vaginal ultrasonography was performed, and serum sex hormone concentrations were measured.

Results: The women taking CBZ or OXC had lower serum testosterone (T) levels and lower free androgen indexes (FAIs) than the control subjects. CBZ medication was associated with increased concentrations of serum sex hormone–binding globulin (SHBG). The patients taking OXC had higher concentrations of dehydroepiandrosterone sulfate (DHEAS) and androstendione (A) than did the women taking CBZ. Moreover, the prevalence of polycystic ovaries (PCOs) was high in the OXC‐treated women.

Conclusions: CBZ and OXC have different effects on the reproductive endocrine function. Although both drugs were associated with low serum T concentrations and low FAIs, only OXC was associated with a high frequency of elevated levels of A and DHEAS and with an increased prevalence of PCOs. These findings suggest that OXC may be disadvantageous for women with epilepsy and hyperandrogenism, whereas CBZ may be beneficial for these women.
Hormone Replacement Therapy in Women with Epilepsy: A Randomized, Double‐Blind, Placebo‐Controlled Study
Authors: Harden Cynthia L. , Herzog Andrew G. , Nikolov Blagovest G. , Koppel Barbara S. , Christos Paul J. , Fowler Kristen , Labar Douglas R. , Hauser W. Allen
Published: June 2006

Summary:  Purpose: Previous reports have suggested that hormone replacement therapy (HRT) could increase seizure activity in women with epilepsy. We sought to determine whether adding HRT to the medication regimen of postmenopausal women with epilepsy was associated with an increase in seizure frequency.

Methods: This was a randomized, double‐blind, placebo‐controlled trial of the effect of HRT on seizure frequency in postmenopausal women with epilepsy, taking stable doses of antiepileptic drugs (AEDs), and within 10 years of their last menses. After a 3‐month prospective baseline, subjects were randomized to placebo, Prempro (0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate or CEE/MPA) daily, or double‐dose CEE/MPA daily for a 3‐month treatment period.

Results: Twenty‐one subjects were randomized after completing baseline. The subjects' ages ranged from 45 to 62 years (mean, 53 years; SD, ±5), and the number of AEDs used ranged from none to three (median, one). Five (71%) of seven subjects taking double‐dose CEE/MPA had a worsening seizure frequency of at least one seizure type, compared with four (50%) of eight taking single‐dose CEE/MPA and one (17%) of six taking placebo (p = 0.05). An increase in seizure frequency of the subject's most severe seizure type was associated with increasing CEE/MPA dose (p = 0.008). An increase in complex partial seizure frequency also was associated with increasing CEE/MPA dose (p = 0.05). Two subjects taking lamotrigine had a decrease in lamotrigine levels of 25–30% while taking CEE/MPA.

Conclusions: CEE/MPA is associated with a dose‐related increase in seizure frequency in postmenopausal women with epilepsy. CEE/MPA may decrease lamotrigine levels.
Characterization of Insulin Secretion in Valproate‐treated Patients with Epilepsy
Authors: Pylvänen Virpi , Pakarinen Arto , Knip Mikael , Isojärvi Jouko
Published: June 2006

Summary:  Purpose: Valproate (VPA) treatment has been reported to be associated with obesity and high fasting serum insulin concentrations in parallel with an unfavorable serum lipid profile and hyperandrogenism and polycystic ovaries in women. The pathogenetic mechanism underlying these changes has remained unknown, although several mechanisms have been implicated.

Methods: Fifty‐one patients receiving monotherapy (31 male and 20 female patients) were included in this study, with 45 (23 male and 22 female) healthy control subjects. These participants were interviewed, clinically examined, and blood samples for fasting plasma glucose, serum insulin, proinsulin, and C‐peptide concentrations were taken after an overnight fast.

Results: The valproate‐treated patients had fasting hyperinsulinemia (11.30 ± 6.23 pM vs. 6.28 ± 4.66 pM in the control subjects; p < 0.001), although the fasting serum proinsulin and C‐peptide concentrations were not significantly higher in the patients than in the control subjects. In addition, proinsulin/insulin (0.30 ± 0.14) and C‐peptide/insulin ratios (35.48 ± 24.09) were lower (p < 0.001) in the VPA‐treated patients when compared with the control subjects (0.53 ± 0.36 and 94.27 ± 61.85, respectively), and they also had lower fasting plasma glucose concentrations (4.72 ± 0.35 mM) than the control subjects (5.12 ± 0.58 mM; p < 0.01).

Conclusions: This study suggests that valproate does not induce insulin secretion but might interfere with the insulin metabolism in the liver, resulting in higher insulin concentrations in the peripheral circulation. These changes are seen irrespective of concomitant weight gain, suggesting that increased insulin concentrations induce weight gain and not vice versa.
Chemical Composition and Structure of the Microcrystals Formed Between Silver(I) and γ‐Hydroxybutyric Acid and γ‐Hydroxyvaleric Acid
Authors: Bell Suzanne C. , Oldfield Lucy S. , Shakleya Diaa M. , Petersen Jeffrey L. , Mercer Jennifer W.
Published: June 2006

ABSTRACT: This study examined microcrystals formed by silver with γ‐hydroxybutyric acid (GHB) and γ‐hydroxyvaleric acid (GHV), the five‐carbon analog of GHB, in the presence of silver, copper, and lanthanide nitrates. Distinct microcrystals formed with silver (+1) and lanthanum (+3) ions but not with the copper (+2) ions. The crystals formed with GHB were distinctly different than those formed with GHV and in all cases, the drug microcrystals were easily distinguishable from reagent crystals. X‐ray diffraction analysis provided definitive structure for the microcrystals. The morphological differences between the silver‐GHB and silver‐GHV crystals were characterized using simple measurements such as size and angles provided by image recognition software. The utility of the test for casework was demonstrated using spiked beverage samples.
Usefulness of Dura Mater in Providing DNA Samples for Identifying Cadavers
Authors: Motani Hisako , Sakurada Koichi , Akutsu Tomoko , Ikegaya Hiroshi , Hayakawa Mutsumi , Sato Yayoi , Yajima Daisuke , Sato Kaoru , Kobayashi Kazuhiro , Iwase Hirotaro
Published: June 2006

ABSTRACT: We examined the usefulness of the dura mater in identifying human remains. Dura mater was collected from 50 cadavers, including drowned, charred, and mummified remains. The STR genotype using the AmpFℓSTR® Identifiler™ Kit could be typed at 15 STR and amelogenin loci in 30 samples of 33 cases. Furthermore, the ABO genotype and amelogenin using gel‐based methods could be typed in 44 samples of 50 cases. In cases with successful typing of STR, ABO‐DNA, and amelogenin, the longest time after death was from 12 to 26 days in a drowned body. The minimum quantity of dura mater required for DNA extraction was about 2.5 mg, dried and fixed by ethanol, in a cadaver 15 h after death. The state of the DNA from the dura mater from the calvaria may be better than that from the basis cranii interna. We found that DNA from dura mater is one of the most useful samples for forensic identification.
The Indirect Detection of Bleach (Sodium Hypochlorite) in Beverages as Evidence of Product Tampering
Authors: Jackson David S. , Crockett David F. , Wolnik Karen A.
Published: June 2006

ABSTRACT: Bleach (sodium hypochlorite) has been identified as the adulterant in a relatively large number of product tamperings that have been investigated by the Forensic Chemistry Center (FCC) of the U.S. Food and Drug Administration. In this work, household bleach was added to 23 different beverages at each of three levels. The impact of sodium hypochlorite on these beverages over a 13‐day study period was evaluated using the following techniques: diphenylamine spot test for oxidizing agents, potassium iodide‐starch test paper for oxidizing agents, pH, iodometric titration for quantitating hypochlorite, ion chromatography for chloride and chlorate quantitation, automated headspace sampling with gas chromatography–flame ionization detection (GC–FID) for determination of chloroform, and visual and organoleptic observations. This study has shown that hypochlorite is fragile when added to most common beverages and typically breaks down either partially or completely over time. In cases where a beverage is suspected of being adulterated with bleach but tests for hypochlorite are negative, it is still possible to characterize the product to demonstrate that the results are consistent with the addition of bleach. An adulterated product will give a positive test for oxidizing agents using the diphenylamine spot test. It is likely that the pH of the adulterated product will be higher than a control of that product. Ion chromatographic analysis shows elevated chloride and chlorate as compared with a control. And, chloroform may also be detected by GC–FID especially if the beverage that was adulterated contains citric acid.
Genetic differentiation between anadromous and freshwater resident brown trout (Salmo truttaL.): insights obtained from stable isotope analysis
Authors: Charles K. , Roussel J.‐M. , Lebel J.‐M. , Baglinière J.‐L. , Ombredane D.
Published: June 2006

Abstract – A genetic survey was carried out on recently emerging fry to investigate interbreeding between anadromous and freshwater resident brown trout in La Roche Brook, a major spawning tributary of the Oir River system (Normandy, France). Emerging fry were sampled at three different sites in spring 2002 and 2003. Stable isotope analysis (SIA) allowed the classification of each individual as the progeny of resident (N = 76) or anadromous (N = 58) female trout. Microsatellite DNA analysis showed that genetic diversity between fry samples can be explained by microgeographical (various sampling sites) and temporal (2 years of sampling) variations rather than maternal origin (anadromous vs. freshwater resident). We conclude that a high level of gene flow exists between the two morphs when anadromous adults have access to the spawning grounds of residents. We highlight the relevance of using SIA in conjunction with genetic analysis to study interactions between the two morphs.
Total proximal tendon avulsion of the rectus femoris muscle
Authors: Irmola T. , Heikkilä J. T. , Orava S. , Sarimo J.
Published: June 2006

Total proximal avulsions of the quadriceps femoris muscle group are rare injuries. Between the years 2001 and 2004 five patients with a total proximal avulsion of the tendon of the rectus femoris muscle were treated surgically in Mehiläinen Hospital in Turku, Finland. The median age of the patients was 21 years (range, 19–27) and the patients were all men. There were four soccer players and one hurdler.

In all cases an avulsion of the proximal tendon of the rectus femoris muscle was confirmed by MRI. All of the patients were operated on and the delay from the injury to surgery ranged from 18 to 102 days.

The result of the surgical treatment was rated good in all cases. All of the patients were able to return to their pre‐injury level of activity 5–10 months after surgery. The median follow‐up time was 20 months (range, 9–38).

Surgical treatment of a total proximal avulsion of the tendon of the rectus femoris muscle seems to result in return to the pre‐injury activity level in most cases.
A prospective study on knee proprioception after meniscal allograft transplantation
Authors: Thijs Y. , Witvrouw E. , Evens B. , Coorevits P. , Almqvist F. , Verdonk R.
Published: June 2006

The meniscus plays an important role in the proprioceptive ability of the knee joint. The aim of this prospective study was to assess the short‐term influence of a meniscus replacement on the proprioception of the knee. Fourteen patients who had undergone a fresh meniscal allograft transplantation between May 2001 and June 2003 were tested pre‐operatively and 6 months post‐operatively. Disability regarding pain, stiffness and functionality of the affected knee during daily activities was measured by the Western Ontario and McMaster Universities Arthritis (WOMAC) scale. The knee joint position sense was assessed using the Biodex System 3®isokinetic dynamometer. The results of the WOMAC scale showed no significant differences concerning pain, stiffness or knee function between the pre‐ and post‐operative condition of the knee. Assessment of the knee joint position sense at a reference point of 70° of knee flexion revealed a significant improvement of the proprioception of the operated knee at 6 months after surgery compared with the pre‐operative condition. The results of this study suggest that although no significant improvement of pain and functionality of the operated knee occurred at this short‐term follow‐up period, a meniscal allograft transplantation seems to have a significant positive effect on the joint position sense of the previously meniscectomised knee.
Multifocal penile intraepithelial neoplasia — targeted treatment with imiquimod
Authors: Dirschka Thomas , Krahl Dieter , Oster‐Schmidt Claus
Published: June 2006

A 78‐year‐old male sought dermatologic consultation for multifocal persistent red lesions of the glans penis. Various topical treatments had proved unsuccessful. Histologic examination revealed penile intraepithelial neoplasia (PIN). Polymerase chain reaction (PCR) showed amplification of human papillomavirus type 16 (HPV‐16) DNA. Urological consultants recommended amputation of the glans; the patient rejected this, as well as any other surgical procedure.

Therefore, he was treated in our dermatologic practice with imiquimod 5 % cream administered daily over 12 weeks. After therapy was completed, no clinical or histologic evidence of residual tumor was found and HPV‐16 DNA was no longer detectable. Local skin reactions such as erosions and edema of the glans accompanied by tingling and itching were well‐tolerated by the patient. Imiquimod 5 % cream may represent an alternative local treatment option for multifocal PIN.
Nocturnal sedation in a child with facial ulceration
Authors: Patel Girish K , Motley Richard J
Published: June 2006

Mostly, herpes zoster affects adults and therefore childhood presentation can represent a diagnostic challenge. Childhood herpes zoster, when it occurs, can also be associated with peripheral nerve complications, as illustrated by this case. A 3‐year‐old child who had herpes zoster developed a nasolabial scar resulting in a shallow non‐healing ulcer from being repeatedly picked. Healing was only achieved after nocturnal sedation, with chloral hydrate.
The management of wounds following primary lower limb arthroplasty: a prospective, randomised study comparing hydrofibre and central pad dressings
Authors: Abuzakuk Tarek M. , Coward Pamela , Shenava Y , Kumar V Senthil , Skinner John A
Published: June 2006

Wound care following lower limb arthroplasty has not been subject to in‐depth clinical research, primarily because such wounds usually heal without complication. However, when prosthetic implants are used, serious wound problems can be disastrous (Whitehouse et al. Infect Control Hosp Epidemiol 2002;23:183–9; Lindwell OM. Clin Orthop Relat Res 1986;211:91–103). We report the results of a prospective, randomised, controlled trial comparing a hydrofibre (Aquacel®) and central pad (Mepore®) dressing in the management of acute wounds following primary total hip or knee arthroplasty left to heal by primary intention. Dressing performance was measured in 61 patients receiving total hip or knee replacements. There was a significant reduction in the requirement for dressing changes before five postoperative days in the hydrofibre group (43% compared with 77% in the central pad group), and there were fewer blisters amongst patients in the hydrofibre group (13% compared with 26% in the central pad group). We conclude that there is a potential role for hydrofibre dressing in the management of arthroplasty wounds.
EXTREMAL k-LIPSCHITZ t-CONORMS
Authors: MESIAROVÁ A.
Published: June 2006

Class of k-Lipschitz t-conorms is shown to have no strongest element for k > 1. Pointwise supremum of the class of k-Lipschitz t-conorms is introduced and the best approximation of this supremum by k-Lipschitz t-conorm is constructed.
MULTIPLICATIVE PROPERTIES IN EVALUATION OF DECISION TREES
Authors: EKENBERG LOVE , DANIELSON MATS , THORBIÖRNSON JOHAN
Published: June 2006

In attempting to address real-life decision problems, where uncertainty about data prevails, some kind of representation of imprecise information is important and several have been proposed. In particular, first-order representations, such as sets of probability measures, upper and lower probabilities, and interval probabilities and utilities of various kinds, have been suggested for enabling a better representation of the input sentences for a subsequent decision analysis. However, sometimes second-order approaches are better suited for modelling incomplete knowledge and we demonstrate how such can add important information when handling aggregations of imprecise representations, as is the case in decision trees or probabilistic networks. Based on this, we suggest a measure of belief density for such intervals. We also demonstrate important properties when operating on general distributions. The results equally apply to approaches which do not explicitly deal with second-order distributions, instead using only first-order concepts such as upper and lower bounds. While the discussion focuses on probabilistic decision trees, the results apply to other formalisms involving products of probabilities, such as probabilistic networks, and to formalisms dealing with products of interval entities such as interval weight trees in multi-criteria decision making.
Multiple positive solutions of Strum‐Liouville equations with singularities
Authors: Wang Zenggui , Liu Lishan , Wu Yonghong
Published: June 2006

The existence of multiple positive solutions for Strum‐Liouville
boundary value problems with singularities is investigated. By
applying a fixed point theorem of cone map, some existence and
multiplicity results of positive solutions are derived. Our
results improve and generalize those in some well‐known results.
Global existence of periodic solutions in a simplified four‐neuron BAM neural network model with multiple delays
Authors: Yan Xiang-Ping , Li Wan-Tong
Published: June 2006

We consider a simplified bidirectional associated memory (BAM)
neural network model with four neurons and multiple time delays.
The global existence of periodic solutions bifurcating from Hopf
bifurcations is investigated by applying the global Hopf
bifurcation theorem due to Wu and Bendixson′s criterion for
high‐dimensional ordinary differential equations due to Li and
Muldowney. It is shown that the local Hopf bifurcation implies the
global Hopf bifurcation after the second critical value of the sum
of two delays. Numerical simulations supporting the theoretical
analysis are also included.
Nonlinear reaction‐diffusion models of self‐organization and deterministic chaos: Theory and possible applications to description of electrical cardiac activity and cardiovascular circulation
Authors: Kardashov V. , Einav Sh. , Okrent Y. , Kardashov T.
Published: June 2006

The paper shows that analytical dynamic models coupled with the available
signal processing methods could be used for describing the
self‐organization and chaos degree in the heartbeats propagation and
pressure pulses in ventricular at ejection phase. We proposed a unit
analytical approach that could be associated with real ECG and pressure
pulses signal processing. Our findings confirm that the real‐time computer
monitoring of the main cardiovascular parameters obtained by the use of
analytical models and verified by signal processing of real clinical data
may be considered as available method for measuring and controlling
self‐organization and chaos degree in pulse propagation.
Nanocrystalline TiO 2 with enhanced photoinduced charge separation as catalyst for the phenol degradation
Authors: Canevali Carmen , Morazzoni Franca , Scotti Roberto , Bellobono Ignazio Renato , Giusti Marco , Sommariva Marco , D′Arienzo Massimiliano , Testino Andrea , Musinu Anna , Cannas Carla
Published: June 2006

Nanocrystalline TiO 2 catalysts based on pure rutile (R100) and
a 30% of anatase and 70% of rutile (R70) were synthesized by the
sol‐gel method, using Pluronic PE 6400 as templating agent.
Catalysts were characterized in terms of structural and
morphological properties; moreover, the formation of paramagnetic
charge carriers under UV irradiation was studied and related to
the activity of TiO 2 in the photoinduced degradation of phenol.
With respect to Degussa P25, the two sol‐gel catalysts show lower
surface area and a wider pore size distribution. The EPR spectra
recorded under UV irradiation show enhanced charge separation in
the sol‐gel samples, with the O − species in higher amount than
in Degussa P25. This result is in agreement with the high
catalytic activity of R100 sample in the photoinduced degradation
of phenol, very similar to that displayed by Degussa P25 and
higher than that of R70 sample.
New variance ratio tests to identify random walk from the general mean reversion model
Authors: Lam Kin , Wong May Chun Mei , Wong Wing-Keung
Published: June 2006

We develop some properties on the autocorrelation of thek-period returns for the general mean reversion (GMR) process in which the stationary component is not restricted to the AR(1) process but takes the form of a general ARMA process. We then derive some properties of the GMR process and three new nonparametric tests comparing the relative variability of returns over different horizons to validate the GMR process as an alternative to random walk. We further examine the asymptotic properties of these tests which can then be applied to identify random walk models from the GMR processes.