bluuebunny/crossref_metadata_2025_split huggingface dataset:
PHARMACOKINETICS AND EFFECTS ON EXERCISE HEART RATE OF PK 11195 (52028 RP), AN ANTAGONIST OF PERIPHERAL BENZODIAZEPINE RECEPTORS, IN HEALTHY VOLUNTEERS
Authors: FERRY A. , JAILLON P. , LECOCQ B. , LECOCQ V. , JOZEFCZAK C. 
Published: August 2009

Summary—PK 11195 (or 52028 RP; 1‐(2‐chlorophenyl)‐N‐methyl‐N‐(1‐methylpropyl)‐3‐isoquinoline carboxamide), an antagonist of the peripheral‐type benzodiazepine receptors which are coupled to calcium channels, was administered to 10 healthy volunteers in order to study the pharmacokinetics and cardiovascular effects of the drug. PK 11195 was randomly administered intravenously (10 mg) and orally in three single dosages (100, 200 and 400 mg). Placebo was only given orally. Heart rate and blood pressure were recorded at rest and during exercise tests which were performed at 0, 1, 3, 6 and 24 h after dosing on each study day.Summary—The results showed that after IV administration, PK 11195 was rapidly distributed in two or three open compartments. Its elimination T1/2was short (3.7 ± 3.0 h) with high interindividual variability. After oral ingestion the pharmacokinetics of PK 11195 were linear over the range of 100–400 mg single oral doses with a stable absolute bioavailability (33%). T1/2elimination was prolonged (7–12 h) and the presence of secondary increases in plasma concentration at 8–10 h and 22–24 h after drug absorption may have been related to enterohepatic cycling. No unchanged PK 11195 could be detected in urine. PK 11195 did not significantly modify heart rate and blood pressure at rest or during exercise and was well tolerated by the subjects. These data suggest a high inter‐individual variability in PK 11195 disposition with extensive metabolism in normal exercising volunteers.
EFFECTS OF ACUTE AND CHRONIC ADMINISTRATION OF TWO ANTIBIOTICS, AZTREONAM AND GENTAMICIN, ALONE OR IN COMBINATION, ON “OPEN‐FIELD TEST” IN MICE
Authors: DE ANGELIS L. 
Published: August 2009

Summary— A study aimed at investigating the behavioural effects of aztreonam and gentamicin, given separately or in combination, was carried out in mice. Animals were randomly assigned to two test conditions: acute and chronic treatment. Those receiving acute treatment had a single IP injection 60 min before the test. Those receiving chronic treatment had IP injections once daily for 5 successive days prior to the test.Behavioural patterns (ambulation, rearing, grooming and defecation) were assessed using the “open‐field” test. The results indicate that, both after single and multiple dosing, aztreonam (10, 40 and 80 mg/kg IP) and/or gentamicin (10 mg/kg IP) do produce changes in the behaviour of animals. A rate increasing effect for certain behaviours (rearing, grooming and defecation) and a reduction in other behaviours (ambulation) seems to occur.
Pharmacokinetics of flunitrazepam following single dose oral administration in liver disease patients compared with healthy volunteers
Authors: Drouet‐Coassolo C. , Iliadis A. , Coassolo P. , Antoni M. , Cano JP 
Published: August 2009

Summary— The pharmacokinetic behaviour of flunitrazepam and its main active metabolite, N‐desmethyl flunitrazepam, was investigated in 12 patients with liver disease (cirrhosis or hepatitis) compared to 6 healthy volunteers. A gas‐liquid chromatographic method allowing for simultaneous determination of flunitrazepam and N‐desmethyl flunitrazepam in plasma samples was developed. The accuracy and the precision near the quantification limit of ca. 1 ng/ml were better than 5%.Plasma levels of flunitrazepam were not significantly altered by hepatic failure, whereas plasma levels of N‐desmethyl flunitrazepam were lower in patients than in heathly subjects. Pharmacokinetic parameters did not differ significantly between healthy subjects and liver disease patients: the oral clearance was 3.5 ± 0.8, 3.5 ± 1.9 and 4.0 ± 1.2 ml/min/kg, respectively in healthy subjects, patients with hepatitis and patients with cirrhosis. The apparent elimination half‐life was 22 ± 5 h in healthy subjects, 25 ± 10 h in patients with hepatitis and 20 ± 6 h in patients with cirrhosis. However, the expected increase of the drug free fraction during liver disease could decrease the therapeutic and toxic ranges of flunitrazepam in these patients.
Effect‐kinetic characterization of dimethindene maleate following oral administration (Fenistil, Tropfen)
Authors: Rehn D. , Geissler H. , Schuster O. , Lukas H. , Hennings G. 
Published: August 2009

Summary— Dimethindene maleate is a well known H1‐receptor antagonist with strong affinity to the H1‐receptor. In order to evaluate the time course of its activity, dimethindene maleate was investigated in a histamine provocation model in man. Eight healthy male volunteers were treated either with 4 mg dimethindene maleate using a commercially available solution (Fenistil, Tropfen) or an identically appearing placebo solution (po) following a double‐blind, crossover study design. Intracutaneous histamine injections were administered at ‐ 1, 2, 5, 14, 17, 20, 23, 26 and 29 h following drug administration. Areas of flares and weals were measured 5, 10, 20, and 30 min following histamine provocation.A strong inhibition of the development of flares and weals was observed to be more pronounced in flares than in weals. Baseline adjusted areas under the curve differ statistically significantly following verum and placebo treatment conditions (P = 0.0028). According to the time schedule of the study maximal effects were observed at time point 5 h. The mean residence times of the inhibitory effects were calculated to be ± 13 h compared to the mean residence times of dimethindene blood levels of ± 8 h indicating a non‐linear relationship between blood level and effect.
CENTRAL NEUROGENIC NEUROPROTECTION: PROTECTION OF BRAIN FROM FOCAL ISCHEMIA BY CEREBELLAR STIMULATION
Authors: Reis DJ , Feinstein D , Galea E , Golanov EV 
Published: August 2009

ABSTRACTElectrical stimulation of the cerebellar fastigial nucleus (FN) elevates regional cerebral blood flow (rCBF) independently of cerebral metabolism (rCGU) throughout brain. One hour of FN stimulation also reduces, by up to 50%, the volume of the focal ischemic infarction produced by occlusion of the middle cerebral artery in rat. Protected areas correspond to the ischemic penumbra. Neuroprotection, while reversible, persists for weeks after 1h of stimulation. It cannot be attributed to increasing rCBF and/or reducing rCGU to improve matching of flow and metabolism. Conditional stimulation of FN initiates long‐lived inhibition of expression of peri‐infarction depolarizing waves, possibly by altering potassium‐channel function and suppresses induction of inducible nitric oxide synthase (iNOS) and ICAM in cerebral microvessels. The brain contains intrinsic networks which may protect the brain from ischemic injury, possibly by producing widespread and longterm suppression of electrical excitability and/or and expression of proinflammatory molecules.
Cardioprotective profile of MET‐88, an inhibitor of carnitine synthesis, and insulin during hypoxia in isolated perfused rat hearts
Authors: Asaka N , Muranaka Y , Kirimoto T , Miyake H 
Published: August 2009

Summary— 3‐(2,2,2‐trimethylhydrazinium) propionate (MET‐88) is an inhibitor of carnitine synthesis. This study was carried out to investigate whether or not reduction of carnitine content could attenuate hypoxic damage in isolated perfused rat hearts.Rats were divided into four groups: 1) vehicle control; 2) pretreatment with MET‐88 (MET‐88); 3) application of insulin (500 μU/mL) in the perfusate (insulin); and 4) pretreatment with MET‐88 and application of insulin (MET‐88 + insulin). MET‐88 (100 mg/kg) was orally administered once a day for 10 days until the day before the experiments. Hearts were initially perfused for a 10 min period under normoxia, followed by a 30 min period under hypoxia. Hearts were frozen at the end of hypoxia for the measurement of high‐energy phosphates, carnitine derivatives, and glycolysis intermediates. In a separate series of untreated and MET‐88 treated hearts, exogenous glucose and palmitate oxidation was measured.MET‐88 decreased the extent of the depression of cardiac contractility (+dP/dt), and aortic flow during the hypoxic state. Insulin also improved cardiac function, and co‐treatment of MET‐88 and insulin additionally improved cardiac function during hypoxia. MET‐88 prevented the decrease of high‐energy phosphate and the increase of long‐chain acylcarnitine after 30 min of hypoxic perfusion. In addition, MET‐88 increased the steady state of glucose oxidation in hypoxic perfused rat hearts. These results indicate that MET‐88 has cardioprotective effects on contractile function and energy metabolism of isolated perfused rat hearts in a hypoxic condition. Preventing the accumulation of long‐chain acylcarnitine may serve to protect hypoxic hearts.
Vitamin E analogues reduce the incidence of ventricular fibrillations and scavenge free radicals
Authors: Walker MK , Vergely C , Lecour S , Abadie C , Maupoil V , Rochette L 
Published: August 2009

Summary— The aim of our study was to analyse the protective effects of different α‐tocopherol analogues 1) against fibrillations induced by an ischemia‐reperfusion sequence, and 2) to further investigate in vitro the radical scavenging properties of these analogues by two sensitive methods. Concerning 1: isolated rat hearts underwent 10 min of coronary ligation followed by reperfusion and the α‐tocopherol analogues were infused IS min before occlusion. Functional parameters including heart rate and fibrillations were recorded. Concerning 2: the β‐phycoerythrin assay was utilised to determine the oxygen radical absorbing capacity (ORAC) of these vitamin E analogues against peroxyl radicals. Electron paramagnetic resonance (EPR) was used to measure their scavenger abilities on hydroxyl radical and superoxide anion production. Concerning 1: ventricular fibrillation times were reduced for all analogues treated hearts at concentrations of 1 μM and 5 μM, with Trolox being the most efficacious. Concerning 2: in our experimental conditions of intense production of free radicals, scavenging IC50 values for hydroxyl radical were 1.15, 2.17 and 4.04 mM for Trolox, MDL 74270 and MDL 74366 respectively. Superoxide anion IC50 values were 1.0 and 6.75 mM for Trolox and MDL 74270.Our results show that water‐soluble analogues of vitamin E are effective in the prevention of coronary ligation induced reperfusion arrhythmia, under our experimental conditions. Moreover, our data demonstrate that these vitamin E analogues are effective scavengers for a variety of radicals. Our studies support the view that compounds that can either inhibit the formation or scavenge free radicals can protect the heart against arrhythmia associated with ischemia‐reperfusion.
Asystole and increased serum myoglobin levels associated with ‘packing blackout’ in a competitive breath‐hold diver
Authors: Andersson Johan P. A. , Linér Mats H. , Jönsson Henrik 
Published: August 2009

SummaryMany competitive breath‐hold divers use ‘glossopharyngeal insufflation’, also called ‘lung packing’, to overfill their lungs above normal total lung capacity. This increases intrathoracic pressure, decreases venous return, compromises cardiac pumping, and reduces arterial blood pressure, possibly resulting in a syncope breath‐hold divers call ‘packing blackout’. We report a case with a breath‐hold diver who inadvertently experienced a packing blackout. During the incident, an electrocardiogram (ECG) and blood pressure were recorded, and blood samples for determinations of biomarkers of cardiac muscle perturbation (creatine kinase‐MB isoenzyme (CK‐MB), cardiac troponin‐T (TnT), and myoglobin) were collected. The ECG revealed short periods of asystole during the period of ‘packing blackout’, simultaneous with pronounced reductions in systolic, diastolic, and pulse pressures. Serum myoglobin concentration was elevated 40 and 150 min after the incident, whereas there were no changes in CK‐MB or TnT. The ultimate cause of syncope in this diver probably was a decrease in cerebral perfusion following glossopharyngeal insufflation. The asystolic periods recorded in this diver could possibly indicate that susceptible individuals may be put at risk of a serious cardiac incident if the lungs are excessively overinflated by glossopharyngeal insufflation. This concern is further substantiated by the observed increase in serum myoglobin concentration after the event.
Relationship between accommodative and vergence dysfunctions and academic achievement for primary school children
Authors: Shin Hoy S. , Park Sang C. , Park Chun M. 
Published: August 2009

AbstractThe purpose of this study was to investigate the prevalence and types of non‐strabismic accommodative and/or vergence dysfunctions in primary school children, and to determine the relationship of these dysfunctions to academic achievement. A total of 1031 parents and their children aged 9–13 years responded to the College of Optometrists in Vision Development Quality of Life (COVD‐QOL) questionnaire. Of these, 258 children whose visual symptom scores were ≥20 were identified for further evaluation. Comprehensive eye and vision examinations were provided to the children who met the eligibility criteria (114 of 258): eligible symptomatic children were those without amblyopia, strabismus, ocular and systemic pathology, and contact lens wear. Children were also excluded if they had visual acuity poorer than 20/25 in either eye or vertical phoria >1 prism diopter. The results showed that 82 of 114 (71.9%) of criteria‐eligible symptomatic primary school children had non‐strabismic accommodative and/or vergence dysfunctions. In addition, a significant relationship was found between these dysfunctions and academic scores in every academic area (reading, mathematics, social science and science) in the total sample. Therefore, accommodative and vergence functions should be tested for all school children who have visual symptoms and/or academic difficulties. Additional study is needed to determine if improvements of accommodative and vergence functions also improve academic achievement.
Oxygen Inhibits Neuronal Activation in the Trigeminocervical Complex After Stimulation of Trigeminal Autonomic Reflex, But Not During Direct Dural Activation of Trigeminal Afferents
Authors: Akerman Simon , Holland Philip R. , Lasalandra Michele P. , Goadsby Peter J. 
Published: August 2009

Objective.— To understand the mechanism of action of oxygen treatment in cluster headache.Background.— Trigeminal autonomic cephalalgias, including cluster headache, are characterized by unilateral head pain in association with ipsilateral cranial autonomic features. They are believed to involve activation of the trigeminovascular system and the parasympathetic outflow to the cranial vasculature from the superior salivatory nucleus (SuS) projections through the sphenopalatine ganglion, via the greater petrosal nerve of the VIIth (facial) cranial nerve. Cluster headache is remarkably responsive to treatment with oxygen, and yet our understanding of its mode of action is unknown.Methods.— Combining models of trigeminovascular nociception and a novel approach that activates the trigeminal‐autonomic reflex, using SuS/facial nerve stimulation, we explored the effect of oxygen on trigeminal nerve activation as well as on autonomic responses through blood flow observations of the lacrimal duct/sac.Results.— Meningeal vasodilation and neuronal firing in the trigeminocervical complex (TCC), in response to dural electrical stimulation, was unaffected by treatment with 100% oxygen. Stimulation of the SuS via the facial nerve caused only marginal changes in dural blood vessel diameter, but did result in evoked firing in the TCC. Two populations of neurons were characterized, those responsive to 100% oxygen treatment, with a maximal inhibition of 33%, 20 minutes after the start of oxygen treatment (t15 = 4.4, P < .0001). A second population of neurons were not inhibited by oxygen and tended to have shorter latency. Oxygen also inhibited evoked blood flow changes in the lacrimal sac/duct caused by SuS stimulation.Conclusions.— The data provide the first systematic, experimental evidence for a mechanism of action of oxygen in cluster headache. The data show oxygen has no direct effect on trigeminal afferents, acting specifically on the parasympathetic/facial nerve projections to the cranial vasculature to inhibit both evoked trigeminovascular activation and activation of the autonomic pathway during cluster headache attacks. Moreover, the studies begin to characterize a novel laboratory model for the most painful primary headache syndrome known – cluster headache.
The Course of Frequent Episodic Migraine in a Large Headache Clinic Population: A 12‐Year Retrospective Follow‐Up Study
Authors: Dahlöf Carl G. H. , Johansson Maria , Casserstedt Susanne , Motallebzadeh Tina 
Published: August 2009

Background.— Despite its high prevalence, little is known about the clinical course of migraine. Presented here are the findings of a 12‐year follow‐up study involving patients diagnosed at baseline with frequent episodic migraine.Objective.— The main objectives were to determine the long‐term outcome of patients with frequent episodic migraine and to identify factors predictive of a favorable vs less favorable prognosis.Methods.— A total of 374 subjects (200 women, 174 men) were selected randomly from a total population of 2812 patients initially diagnosed before December 31, 1996, with episodic migraine and at baseline experiencing 1 to 6 attacks per month. Their subsequent migraine course was evaluated via telephone interviews conducted between 2005 and 2006.Results.— Migraine attacks had ceased in 110 (29%) of the 374 patients (57 women and 53 men). The remaining 264 subjects continued to experience migraine attacks at follow‐up, and a change in attack frequency was reported by 80% (of whom 80% reported fewer attacks). Sixty‐six percent reported a change in pain intensity over time, and of these 83% reported milder pain. Only 6 subjects (6/374 = 1.6%) had developed chronic migraine.Conclusion.— These data from a headache clinic population suggest that migraine has a favorable prognosis in most patients. Whether the findings reflect the natural history of the disorder or interval improvements in headache management remains conjectural.
TAXONOMIC REEXAMINATION OF CHARA GLOBULARIS (CHARALES, CHAROPHYCEAE) FROM JAPAN BASED ON OOSPORE MORPHOLOGY AND rbcL GENE SEQUENCES, AND THE DESCRIPTION OF C. LEPTOSPORA SP. NOV.1
Authors: Sakayama Hidetoshi , Kasai Fumie , Nozaki Hisayoshi , Watanabe Makoto M. , Kawachi Masanobu , Shigyo Mikao , Nishihiro Jun , Washitani Izumi , Krienitz Lothar , Ito and Motomi 
Published: August 2009

Chara globularis Thuillier (=f. globularis sensu R. D. Wood) is a widespread species of the genus and inhabits fresh‐ and brackish‐water environments. In an attempt to reexamine the taxonomic status of C. globularis collected from Japan, we reassessed vegetative and oospore morphology of Japanese material and herbarium specimens originating from Europe (including the type specimen) and conducted molecular phylogenetic analyses based on rbcL gene sequences. Although the other vegetative morphologies were consistent with the description of C. globularis f. globularis sensu R. D. Wood, we identified two types of branchlets within the Japanese materials: one has elongate end segments (EL type), and the other has short end segments (SH type) corresponding to the type material. Moreover, the oospore wall of the EL type was different from that in the SH type. The oospores of the EL type were dark brown to reddish brown and had a spongy pattern with the pusticular elevations on the fossa wall, whereas the fossa wall of the SH type was black with a granulate to papillate or fine pusticular pattern. In addition, our sequence data demonstrated that these two types are separated phylogenetically from each other. Therefore, we describe the EL type as a new species, C. leptospora sp. nov.
FIRST INDUCED PLASTID GENOME MUTATIONS IN AN ALGA WITH SECONDARY PLASTIDS: psbA MUTATIONS IN THE DIATOM PHAEODACTYLUM TRICORNUTUM (BACILLARIOPHYCEAE) REVEAL CONSEQUENCES ON THE REGULATION OF PHOTOSYNTHESIS1
Authors: Materna Arne C. , Sturm Sabine , Kroth Peter G. , Lavaud Johann 
Published: August 2009

Diatoms play a crucial role in the biochemistry and ecology of most aquatic ecosystems, especially because of their high photosynthetic productivity. They often have to cope with a fluctuating light climate and a punctuated exposure to excess light, which can be harmful for photosynthesis. To gain insight into the regulation of photosynthesis in diatoms, we generated and studied mutants of the diatom Phaeodactylum tricornutum Bohlin carrying functionally altered versions of the plastidic psbA gene encoding the D1 protein of the PSII reaction center (PSII RC). All analyzed mutants feature an amino acid substitution in the vicinity of the QB‐binding pocket of D1. We characterized the photosynthetic capacity of the mutants in comparison to wildtype cells, focusing on the way they regulate their photochemistry as a function of light intensity. The results show that the mutations resulted in constitutive changes of PSII electron transport rates. The extent of the impairment varies between mutants depending on the proximity of the mutation to the QB‐binding pocket and/or to the nonheme iron within the PSII RC. The effects of the mutations described here for P. tricornutum are similar to effects in cyanobacteria and green microalgae, emphasizing the conservation of the D1 protein structure among photosynthetic organisms of different evolutionary origins.
LOW THERMAL LIMIT OF GROWTH RATE OF SYMBIODINIUM CALIFORNIUM (DINOPHYTA) IN CULTURE MAY RESTRICT THE SYMBIONT TO SOUTHERN POPULATIONS OF ITS HOST ANEMONES (ANTHOPLEURA SPP.; ANTHOZOA, CNIDARIA)1
Authors: McBride Brooke Baldauf , Muller‐Parker Gisèle , Jakobsen Hans Henrik 
Published: August 2009

Symbiodinium californium (#383, Banaszak et al. 1993) is one of two known dinoflagellate symbionts of the intertidal sea anemones Anthopleura elegantissima, A. xanthogrammica, and A. sola and occurs only in hosts at southern latitudes of the North Pacific. To investigate if temperature restricts the latitudinal distribution of S. californium, growth and photosynthesis at a range of temperatures (5°C–30°C) were determined for cultured symbionts. Mean specific growth rates were the highest between 15°C and 28°C (μ 0.21–0.26 · d−1) and extremely low at 5, 10, and 30°C (0.02–0.03 · d−1). Average doubling times ranged from 2.7 d (20°C) to 33 d (5, 10, and 30°C). Cells cultured at 10°C had the greatest cell volume (821 μm3) and the highest percentage of motile cells (64.5%). Growth and photosynthesis were uncoupled; light‐saturated maximum photosynthesis (Pmax) increased from 2.9 pg C · cell−1 · h−1 at 20°C to 13.2 pg C · cell−1 · h−1 at 30°C, a 4.5‐fold increase. Less than 11% of daily photosynthetically fixed carbon was utilized for growth at 5, 10, and 30°C, indicating the potential for high carbon translocation at these temperatures. Low temperature effects on growth rate, and not on photosynthesis and cell morphology, may restrict the distribution of S. californium to southern populations of its host anemones.