bluuebunny/crossref_metadata_2025_split huggingface dataset:
Co‐expression of non‐selective cation channels of the transient receptor potential canonical family in central aminergic neurones
Authors: Sergeeva Olga A. , Korotkova Tatiana M. , Scherer Annette , Brown Ritchie E. , Haas Helmut L. 
Published: June 2003

AbstractThe mammalian transient receptor potential canonical (TRPC) group of channels is a family of Ca2+‐permeable cation channels that are activated following receptor‐mediated stimulation of different isoforms of phospholipase C. In vitro TRPC proteins can form hetero‐ or homo‐oligomeric channels. We performed single‐cell RT–PCR analysis to reveal the co‐expression of seven TRPC channels in identified rat aminergic neurones. All serotonergic neurones of the dorsal raphe (DR), the majority of histaminergic (tuberomamillary nucleus; TMN) and dopaminergic cells of the ventral tegmental area (VTA), as well as some GABAergic neurones from the VTA, expressed at least one variant of TRPC channels. No TRPC channel expression was found in the locus coeruleus. In raphe neurones TRPC6 and TRPC5 mRNAs occurred most frequently. In VTA and TMN co‐expression of TRPC4 with TRPC5 and TRPC6 with TRPC7 was not found in individual neurones (in contrast to the whole‐brain regions). Their co‐expression in non‐neuronal cells could not be excluded. The neonatal TRPC3 subunit was rarely seen. In DR, but not in the other nuclei studied, the expression of orexin receptors correlated with the expression of TRPC channels. We conclude that several TRPC channel populations exist in individual neurones and that their subunit co‐expression pattern is region and cell‐type specific.
Chronic lithium administration potentiates brain arachidonic acid signaling at rest and during cholinergic activation in awake rats
Authors: Basselin Mireille , Chang Lisa , Seemann Ruth , Bell Jane M. , Rapoport Stanley I. 
Published: June 2003

AbstractStudies were performed to determine if the reported ‘proconvulsant’ action of lithium in rats given cholinergic drugs is related to receptor‐initiated phospholipase A2 signaling via arachidonic acid. Regional brain incorporation coefficients k* of intravenously injected [1‐14C]arachidonic acid, which represent this signaling, were measured by quantitative autoradiography in unanesthetized rats at baseline and following administration of subconvulsant doses of the cholinergic muscarinic agonist, arecoline. In rats fed LiCl for 6 weeks to produce a therapeutically relevant brain lithium concentration, the mean baseline values of k* in brain auditory and visual areas were significantly greater than in rats fed control diet. Arecoline at doses of 2 and 5 mg/kg intraperitoneally increased k* in widespread brain areas in rats fed the control diet as well as the LiCl diet. However, the arecoline‐induced increments often were significantly greater in the LiCl‐fed than in the control diet‐fed rats. Lithium's elevation of baseline k* in auditory and visual regions may correspond to its ability in humans to increase auditory and visual evoked responses. Additionally, its augmentation of the k* responses to arecoline may underlie its reported ‘proconvulsant’ action with cholinergic drugs, as arachidonic acid and its eicosanoid metabolites can increase neuronal excitability and seizure propagation.
Truncated beta‐amyloid peptide species in pre‐clinical Alzheimer's disease as new targets for the vaccination approach
Authors: Sergeant Nicolas , Bombois Stepanie , Ghestem Antoine , Drobecq Hervé , Kostanjevecki Vesna , Missiaen Carla , Wattez Annick , David Jean‐Phillipe , Vanmechelen Eugeen , Sergheraert Christian , Delacourte André 
Published: June 2003

AbstractVaccination against human beta‐amyloid peptide (Aβ) has been shown to remove the amyloid burden produced in transgenic mice overexpressing the mutated human amyloid precursor protein (APP) gene. For human beings, the efficiency of this therapeutic strategy has to take into account the specificities of human amyloid, especially at the early stages of ‘sporadic’ Alzheimer's disease (AD). Aβ 40/42 were previously quantified in tissues from our well‐established brain bank, including non‐demented individuals with both mild amyloid and tau pathologies, hence corresponding to the earliest stages of Alzheimer pathology. Herein, we have adapted a proteomic method combined with western blotting and mass spectrometry for the characterization of insoluble Aβ extracted in pure‐formic acid. We demonstrated that amino‐truncated Aβ species represented more than 60% of all Aβ species, not only in full blown AD, but also, and more interestingly, at the earliest stage of Alzheimer pathology. At this stage, Aβ oligomers were exclusively made of Aβ‐42 species, most of them being amino‐truncated. Thus, our results strongly suggest that amino‐truncated Aβ‐42 species are instrumental in the amyloidosis process. In conclusion, a vaccine specifically targeting these pathological amino‐truncated species of Aβ‐42 are likely to be doubly beneficial, by inducing the production of specific antibodies against pathological Aβ products that are, in addition, involved in the early and basic mechanisms of amyloidosis in humans.
Gastrointestinal effects of nonsteroidal anti‐inflammatory drugs
Authors: Whittle Brendan J. R. 
Published: June 2003

AbstractNon‐steroidal anti‐inflammatory drugs (NSAIDs) causes extensive damage to the gastrointestinal (GI) tract. The underlying mechanisms of gastric injury include topical irritant actions that disrupt the epithelial barrier, as well as the inhibition of cyclo‐oxygenase (COX), which is predominantly the COX‐1 isoform in the mucosa. This damage can be attenuated by antisecretory agents or by mucosal protective agents such as the synthetic prostanoids or nitric oxide (NO) donors. Compounds designed to attenuate topical irritancy, or have protective agents incorporated, such as NO‐containing NSAIDs, the CINODs (cyclo‐oxygenase‐inhibiting NO‐donating drugs) show reduced mucosal injury. NSAIDs also cause injury in the small intestine, which appears to result from initial COX inhibition, with subsequent translocation of indigenous bacteria, induction of NO synthase and production of the cytotoxic moiety, peroxynitrite. The COX‐2 selective agents, the coxibs, which inhibit prostanoid biosynthesis at inflammatory sites, but not the endogenous protective prostanoids in the gut formed by COX‐1, have proved so far to be a successful therapeutic approach to reducing NSAIDs GI damage. The clinical outcome of the use of the second generation of coxibs, and the newer NO NSAIDs is now awaited.
Different vascular responsiveness to angiotensin II in two normotensive rat strains
Authors: Herin Laetitia , Blanc Jocelyne , Basset Alexandra , Laude Dominique , Laurent Stéphane , Elghozi Jean‐Luc 
Published: June 2003

AbstractRats of the Fischer 344 (F344) and Wistar Kyoto (WKY) strains are known to present differences in stimuli responses involving the renin–angiotensin system and in cardiovascular responses to an acoustic startle stimulus. Here we compared the vascular reactivity to angiotensin II (ANG II) of these normotensive, inbred rat strains.  Blood pressure (BP) and heart rate (HR) were recorded in conscious rats, before and after a neurohumoral blockade obtained by successive administration of chlorisondamine, enalapril, a V1‐vasopressinergic receptor antagonist (Manning compound) and atropine methyl nitrate. BP was restored by a constant infusion of noradrenaline. Boluses of ANG II ranging from 0.001 to 1280 ng/kg were injected randomly. Average dose–response curves were established. After neurohumoral blockade, the minimum mean BP (MBP) produced by hydralazine (3 mg/kg, i.v.) and the maximum MBP produced by noradrenaline (60 μg/mL and 800 μL/min, i.v.) were used to reflect arterial wall structure.

The maximal systolic blood pressure (SBP) and pulse pressure (PP) responses to ANG II were higher in F344 compared with WKY (+86 ± 3 mmHg vs. +71 ± 3 mmHg, P < 0.01 for SBP, +31 ± 2 mmHg vs. +18 ± 1 mmHg, P < 0.001 for PP). After the ANG II type 1 (AT1) receptor blocker valsartan, ANG II had no significant effect on BP. F344 and WKY exhibited the same maximum MBP in response to noradrenaline. However, MBP level following hydralazine was higher in F344 (F344: 48 ± 2 mmHg vs. WKY: 37 ± 3 mmHg, P < 0.01).

The amplification in F344 of the vasoconstrictive response to ANG II mediated by AT1 receptors is compatible with a high number of AT1 receptors in this strain. In F344, the exaggerated systolic and PP responses to ANG II and the higher MBP level after hydralazine most likely reflect a structural modification of the arterial wall such as hypertrophic remodelling in F344.
Frequency of cytochrome P450 2C9 allelic variants in the Chinese and French populations
Authors: Yang Jue Quin , Morin Sandrine , Verstuyft Céline , Fan Li An. , Zhang Yong , Xu Chun Di , Barbu Véronique , Jaillon Patrice , Becquemont Laurent 
Published: June 2003

AbstractCytochrome P450 2C9 (CYP2C9) is a polymorphic enzyme responsible for the metabolism of different drugs with low therapeutic index such as oral anticoagulants. CYP2C9*2 and CYP2C9*3 are two single nucleotide polymorphic allelic variants. The frequency of these alleles in different ethnic populations is extremely variable. In this study, we compared the frequencies of CYP2C9 allelic variants among 394 Chinese living in Shanghai to 151 French Caucasians living in Paris. The allelic frequencies of CYP2C9 variants of the Chinese and the French subjects were 0.963, 0.001, 0.036 and 0.77, 0.15, 0.08 for CYP2C9*1, CYP2C9*2, CYP2C9*3, respectively. Chinese CYP2C9*3 allelic frequency was twice as lower as the French subjects, but three times higher than Korean (0.036 vs. 0.011). The CYP2C9*2 allele could be detected in only one Chinese subject, whereas it represented the major allelic variant in French Caucasians. The low frequency of the CYP2C9*2 and CYP2C9*3 allelic variants in Chinese subjects does not justify their detection in clinical practice, unlike French Caucasians.
Effect of drugs on cholesterol crystallization in an artificial bile model and relation of this effect to drug binding to albumin
Authors: Šmídková Markéta , Špundová Marcela , Mareček Zdeněk , Entlicher Gustav 
Published: June 2003

AbstractSubstances that can affect the crystallization of cholesterol from human bile and consequently the gallstone formation have been given considerable attention. We improved the model system for testing cholesterol crystallization‐affecting activity (promoting or inhibiting) of substances and used it for some drugs that are excreted into bile. Besides other factors natural lipid–protein complexes isolated from the native human bile have been shown to be responsible for nucleation and fast crystal growth in cholesterol supersaturated model bile. Artificial lipid–protein complex of taurolithocholate, human serum albumin and Ca2+ (TLTC–HSA–Ca2+) exhibited a lower crystallization activity than both the artificial lipid–protein complexes of taurodeoxycholate, human serum albumin and Ca2+ and the lipid–protein complex isolated from native human bile. The model bile supplemented with this artificial lipid–protein complex (TLTC–HSA–Ca2+) formed a convenient system for testing of various substances (drugs) for their crystallization‐affecting activity. From the 20 tested drugs, which could occur at least in small amounts in human bile, the highest crystallization‐promoting activity was found for complexes with ampicillin, butorphanol and colchicine. Complexes with tetracycline, thioridazine and doxycycline were the strongest inhibitors.The drugs, which had some effect on cholesterol crystallization, affected somehow the artificial lipid–albumin complex by displacing its components. Interactions of different drugs with HSA and its artificial complexes with the conjugated bile salt and Ca2+ ions were followed by absorption spectroscopy to observe displacement interactions. On the basis of these experiments we could classify drugs into four groups which differ by their effects on spectral characteristics of complexes.
Twelve‐hour shift on ITU: a nursing evaluation
Authors: Richardson Annette , Dabner Nichola , Curtis Sarah 
Published: June 2003

Summary

This paper describes the introduction and subsequent evaluation of a 12‐h shift system in a large ITU in the northeast of UK
To date, only a small number of studies has evaluated nurses working the 12‐h shifts in critical care areas
To evaluate the level of staff satisfaction, data were collected by means of a questionnaire involving 41 nurses, at 3 months following the introduction of the 12‐h shifts
The responses from the evaluation advocated the continuation of 12‐h shifts with alternative shift patterns for nurses who felt dissatisfied with the current system
Twelve‐hour shifts can be seen as a flexible system for nurses working in intensive care and may assist with staff satisfaction and improving nurse recruitment and retention
Nursing care of the acute head injury: a review of the evidence
Authors: Price Ann M , Collins Timothy J , Gallagher Alison 
Published: June 2003

SUMMARY

This article aims to review the current evidence in relation to acute head injury care
Head injuries are a frequent cause of death and disability in western society with the first 72 h being an important period for prevention of further brain damage
The underlying physiology behind head injury and intracranial pressure will be discussed
The monitoring of intracranial pressure and implications for practice will be addressed
The specialized nursing care and drug therapy management that is necessary for acute head injury patients will be highlighted
Recommendations for practice will be given
Catecholaminergic Innervation of the Human Dura Mater Involved in Headache
Authors: Cavallotti Daniela , Artico Marco , De Santis Stefano , Iannetti Giandomenico , Cavallotti Carlo 
Published: June 2003

The catecholaminergic innervation of cranial dura mater in humans was studied by examining several dural zones (vascular, perivascular, intervascular) in different regions (basal, calvarial, occipital, frontal, tentorial, parietal, temporal).The results demonstrate that catecholaminergic nerve fibers are present in human cranial dura mater and that these fibers, after exposure to formaldehyde vapors, show the specific fluorescence of catecholamines.There are more dural catecholaminergic nerve fibers in the basal region than in the calvarial region. Moreover, these nerve fibers are more abundant in the perivascular dural zone than in the intervascular zone.We hypothesize that these catecholaminergic nerve fibers may be involved in headache.
SUNCT Syndrome. Two Cases in Argentina
Authors: Raimondi Elsa , Gardella Lorenzo 
Published: June 2003

Two patients suffering from SUNCT syndrome are presented. Some features are remarkable. The first patient was a 69‐year‐old man whose first crisis was located in the right supraorbital region. After a 4‐month spontaneous remission, the pain returned to the upper part of the cheek, radiating to the supraciliary region on the same side, with lacrimation and conjunctival injection. Rhinorrhea was absent The painful attacks were triggered by head movements. Clinical improvement occurred with carbamazepine treatmentThe second patient was a 48‐year‐old woman whose painful attacks lasted from 30 to 45 seconds followed by a burning sensation lasting 2 hours. Autonomic signs such as conjunctival injection, lacrimation, and edema and ipsilateral ptosis of the upper lid were rather marked. There was never any rhinorrhea. Her attacks were triggered by head and eye movements. She responded to the administration of corticosteroids and carbamazepine.According to these features, the two patients had SUNCT syndrome, and the positive carbamazepine response suggests a relationship with trigeminal neuralgia.
Acute glucose deprivation leads to apoptosis in a cell model of acute diabetic neuropathy
Authors: Honma Hiroyuki , Podratz Jewel L. , Windebank And Anthony J. 
Published: June 2003

Abstract Objective:  Our aims were to better understand the mechanisms underlying peripheral neuropathy with diabetes mellitus and to test the hypothesis that acute lowering of glucose levels induces apoptosis in hypoxic neurons.Methods:  We used rat dissociated dorsal root ganglion (DRG) neurons incubated in a medium high in glucose concentration (700 mg%) and room air (PO2 150 torr). After 5 days, DRG neurons were placed in hypoxic conditions (PO2 7.6 torr) with a normal‐glucose (100 mg%) or high‐glucose (700 mg%) medium containing 3 or 100 ng/mL of nerve growth factor. Acute lowering of glucose levels under hypoxic conditions led to apoptosis of DRG neurons. Apoptosis was demonstrated by bis‐benzimide staining for nuclear fragmentation, electron microscopy, DNA laddering, and TUNEL staining. Caspase 3 immunocytochemistry and inhibition of neuronal death by the caspase inhibitor z‐VAD‐fmk (100 μM) confirmed that death was apoptotic.Results:  Hypoxia‐induced death was decreased when DRG neurons were maintained in high‐glucose medium, suggesting that high levels of substrate protected against hypoxia. Apoptosis was completely prevented by increasing the concentration of nerve growth factor from 3 to 100 ng/mL and was partially prevented by the addition of the antioxidant α‐lipoic acid (500 μM).Conclusions:  This model provides a novel means for studying the pathogenesis and treatment of early stages of diabetic neuropathy.
Clinical Usefulness of Electrophysiologic Testing in Patients with Ventricular Tachycardia and Chronic Chagasic Cardiomyopathy Treated with Amiodarone or Sotalol
Authors: Leite Luiz R. , Fenelon Guilherme , Simoes Aloyr , Silva Georgia G. , Friedman Paul A. , Paola Angelo A.V. de 
Published: June 2003

Introduction: This study assessed the role of electrophysiologic testing to identify therapeutic strategies for the treatment of patients with sustained ventricular tachycardia (VT) and chronic chagasic cardiomyopathy treated with amiodarone or sotalol.
Methods and Results: One hundred fifteen patients [69 men (60%); mean age

52 ± 10

years] with chagasic cardiomyopathy presenting with symptomatic VT were studied after loading with Class III antiarrhythmic drugs; 78 had a history of sustained VT, and 37 with symptomatic nonsustained VT had sustained VT induced at baseline electrophysiologic study. All but 12 patients also underwent baseline electrophysiologic study. Mean left ventricular ejection fraction was

0.49 ± 0.14
. Based on results of electrophysiologic study after loading with Class III drugs, patients were divided into three groups: group 1(n = 23)had no sustained VT induced; group 2(n = 45)had only tolerated sustained VT induced; and group 3(n = 47)had hemodynamically unstable sustained VT induced. After a mean follow‐up of52 ± 32months, total mortality rate was 39.1%; it was significantly higher in group 3 than in groups 2 and 1 [69%, 22.2%, and 26%, respectively, P < 0.0001, hazard ratio (HR) 10.4, 95% confidence interval (CI) 3.8, 21.8]. There was no significant difference in total mortality rate between groups 1 and 2 (P = 0.40, HR 1.5, 95% CI 0.75, 4.58). Cardiac mortality and sudden cardiac death rates also were higher in group 3 patients.
Conclusion: In patients with chagasic cardiomyopathy and sustained VT, electrophysiologic testing can predict long‐term efficacy of Class III antiarrhythmic drugs. This may help in the selection of patients for implantable cardioverter defibrillator therapy. (J Cardiovasc Electrophysiol, Vol. 14, pp. 567‐573, June 2003)
Blockade of the Inward Rectifying Potassium Current Terminates Ventricular Fibrillation in the Guinea Pig Heart
Authors: Warren Mark , Guha Prabal K. , Berenfeld Omer , Zaitsev Alexey , Anumonwo Justus M.B. , Dhamoon Amit S. , Bagwe Suveer , Taffet Steven M. , Jalife José 
Published: June 2003

Introduction: Stable high‐frequency rotors sustain ventricular fibrillation (VF) in the guinea pig heart. We surmised that rotor stabilization in the left ventricle (LV) and fibrillatory conduction toward the right ventricle (RV) result from chamber‐specific differences in functional expression of inward rectifier (Kir2.x) channels and unequal IK1 rectification in LV and RV myocytes. Accordingly, selective blockade of IK1 during VF should terminate VF.
Methods and Results: Relative mRNA levels of Kir2.x channels were measured in LV and RV. In addition, LV

(n = 21)

and RV

(n = 20)

myocytes were superfused with BaCl2 (5–50 μmol/L) to study the effects on IK1. Potentiometric dye‐fluorescence movies of VF were obtained in the presence of Ba2+

(0–50 μmol/L)

in 23 Langendorff‐perfused hearts. Dominant frequencies (DFs) were determined by spectral analysis, and singularity points were counted in phase maps to assess VF organization. mRNA levels for Kir2.1 and Kir2.3 were significantly larger in LV than RV. Concurrently, outward IK1 was significantly larger in LV than RV myocytes. Ba2+ decreased IK1 in a dose‐dependent manner (LV change > RV change). In baseline control VF, the fastest DF domain

(28–40 Hz)

was located on the anterior LV wall and a sharp LV‐to‐RV frequency gradient of

21.2 ± 4.3 Hz

was present. Ba2+ significantly decreased both LV frequency and gradient, and it terminated VF in a dose‐dependent manner. At 50 μmol/L, Ba2+ decreased the average number of wavebreaks (

1.7 ± 0.9

to

0.8 ± 0.6 SP/sec · pixel, P < 0.05

) and then terminated VF.
Conclusion: The results strongly support the hypothesis that IK1 plays an important role in rotor stabilization and VF dynamics. (J Cardiovasc Electrophysiol, Vol. 14, pp. 621‐631, June 2003)
LocaLisa Catheter Navigation Reduces Fluoroscopy Time and Dosage in Ablation of Atrial Flutter:
Authors: Schneider Michael A.E. , Ndrepepa Gjin , Dobran Ildiko , Schreieck Jürgen , Weber Stefan , Plewan Andreas , Deisenhofer Isabel , Karch Martin R. , Schömig Albert , Schmitt Claus 
Published: June 2003

Introduction: Catheter ablation has become a well‐established therapy for isthmus‐dependent right atrial flutter (AFL). Recently, mapping and ablation of AFL have been performed using sophisticated three‐dimensional mapping systems, such as electroanatomic and noncontact mapping systems. The LocaLisa system enables nonfluoroscopic navigation of intracardiac electrode catheters based on impedance changes related to catheter movements in transthoracic current fields. The aim of this randomized prospective study was to compare the efficacy of the LocaLisa system with the conventional mapping/ablation approach for radiofrequency ablation of AFL.
Methods and Results: Fifty consecutive patients with AFL (39 men and 11 women; age

65 ± 10

years) were studied. The patients were randomly assigned to undergo radiofrequency ablation guided by a conventional fluoroscopy‐based approach (24 patients) or by the LocaLisa system (26 patients). Ablation success rate and documentation of bidirectional isthmus block were 100% in both groups. Compared with fluoroscopy‐guided approaches, LocaLisa‐guided procedures demonstrated a reduction in total fluoroscopy time from

15.9 ± 10.6

minutes to

7.5 ± 6.5 minutes (P < 0.005).

Total fluoroscopy dosage was reduced from

21.0 ± 19.8

to

8.7 ± 9.5 Gycm2 (P < 0.05).

Fluoroscopy time required for ablation was significantly shortened in the LocaLisa group

(2.6 ± 2.6 min)

compared with the conventional approach group

(11 ± 10 min, P < 0.0005).

In 9 (35%) of 26 patients, the ablation could be performed with a fluoroscopy time ≤1 minute. There were no significant differences with regard to the number of radiofrequency applications, fluoroscopy time needed for diagnostic reasons, total procedure time, or other ablation data.
Conclusion: Compared with the conventional approach, the LocaLisa system significantly reduces the fluoroscopy times needed for ablation of typical AFL.
(J Cardiovasc Electrophysiol, Vol. 14, pp. 587‐590, June 2003)