bluuebunny/crossref_metadata_2025 huggingface dataset:
Enzyme induction and inhibition by new antiepileptic drugs: a review of human studies
Authors: Benedetti Margherita Strolin
Published: August 2009

Abstract—The aim of this paper is to review a number of new antiepileptic agents (i.e. felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate, vigabatrin and zonisamide) for their inducing and/or inhibitory properties in humans, mainly considering the interactions where they are involved as the cause rather than the object of such interactions. Two aspects have been particularly taken into account: the changes or absence of changes in plasma/serum concentrations of concomitant drugs and the direct or indirect evidence of induction, inhibition or lack of effect on the six major human hepatic CYP isozymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4), as well as on other CYP isozymes or enzyme systems. Felbamate clearly affects the pharmacokinetics of a number of drugs, generally increasing but also decreasing their concentrations. It induces enzymes such as CYP3A4 and inhibits enzymes such as CYP2C19 and those of the β‐oxidation pathway. Topiramate is not devoid of potential interaction properties: it decreases the plasma concentrations of ethinylestradiol, induces CYP3A4 and inhibits CYP2C19. For oxcarbazepine, no inhibitory, only inductive effects have been observed thus far. Felbamate, topiramate and oxcarbazepine may induce the metabolism of steroidal oral contraceptives. In this respect, tiagabine has been studied at a rather low dose. Pharmacodynamic or pharmacokinetic interaction seems to exist between lamotrigine and carbamazepine. Lamotrigine appears to be a weak inducer of UGTs, whereas induction of CYP3A4 seems improbable as the compound does not change the concentrations of oral contraceptives or the urinary excretion of 6β‐hydroxycortisol. Zonisamide has very peculiar pharmacokinetics and an extensive metabolism. Additional information on its enzyme inducing or inhibiting properties would be necessary, as data so far collected on its effect on the pharmacokinetics of other drugs are conflicting. Gabapentin, vigabatrin and in particular levetiracetam appear to be devoid of significant enzyme inducing or inhibiting properties.
Effect of acute atenolol on short‐term blood pressure variability and baroreflex sensitivity in rats
Authors: Neto Edmundo Pereira de Souza , Frutoso Jean , Somody Laurence , Gharib Claude , Fortrat Jacques‐Olivier
Published: August 2009

Abstract—Beta‐blocker therapy for hypertension or coronary artery disease is common, but there are a lot of controversies about its effects on short‐term blood pressure variability and arterial baroreceptor reflexes. The aim of this study was to evaluate the effects of acute atenolol on baroreflex sensitivity (BRS) and on the spontaneous variability of systolic blood pressure (SBP) and RR intervals in conscious rats. Ten Wistar rats equipped with telemetry system were evaluated: 1) under control conditions; 2) after injection of saline; and 3) during β1‐adrenergic blockade by atenolol. Fast Fourier transform analysis was applied to RR intervals and SBP. Atenolol increased RR intervals significantly by 14% and the variation coefficient of the RR intervals by 31%. SBP was reduced significantly by 9%. In frequency domain, β1‐blockade in RR intervals increased very low frequency by 33% and the total power by 22% and decreased low frequency by 25%. The ratio of low to high frequency power decreased by 60%. Frequency domain variables in SBP were not significantly changed after β1‐adrenergic receptor blockade. BRS (gain α) was not significantly altered by beta‐blockers. Acute atenolol decreased SBP and increased RR intervals with no change in BRS, indicating ‘resetting’ of baroreflex function.
Effects of pimobendan, a new cardiotonic agent, on contractile responses in single skeletal muscle fibres of the frog
Authors: Wakisaka C. , Kitamura N. , Ohta T. , Kai T. , Nakazato Y. , Ito S.
Published: August 2009

Abstract— Effects of a new cardiotonic agent, pimobendan, on contraction were investigated in single intact skeletal muscle fibres of the frog. Pimobendan increased twitch tension in a concentration‐dependent manner regardless of the presence or absence of Ca2+without any effect on tetanic tension, the resting membrane potential and the shape of the action potential. Pimobendan caused a further increase in twitch tension potentiated by caffeine (1 mM). Adenine, an inhibitor of Ca2+‐induced Ca2+release from the sarcoplasmic reticulum, inhibited twitch tension potentiated by caffeine but not by pimobendan, suggesting that twitch potentiation by pimobendan is not attributed to increases in Ca2+‐induced Ca2+release. Pimobendan failed to increase cAMP levels in the skeletal muscle, though forskolin significantly increased it without any effect on twitch tension. Contractile responses to high concentrations of caffeine and K+were also potentiated by pimobendan. These results suggest that the potentiating effect of pimobendan on skeletal muscle contraction is mainly due to the increase in Ca2+sensitivity to the contractile apparatus.
Activity of ebastine (10 and 20 mg) and cetirizine at 24 hours of a steady state treatment in the skin of healthy volunteers
Authors: Frossard Nelly , Benabdesselam Ouardia , Purohit Ashok , Mounedji Nadjat , Pauli Gabrielle
Published: August 2009

Abstract— We have compared the inhibitory effects of ebastine (10 mg), ebastine (20 mg) and cetirizine (10 mg) on histamine‐induced wheal and flare skin reactions 24 h following a 6‐day‐long treatment. This was a double‐blind, randomised, crossover, placebo‐controlled study involving 24 healthy volunteers (18–65 years) with negative skin prick tests and the absence of specific IgEs to common allergens. Subjects were randomised to receive each of the following treatments once daily for 6 days: ebastine (10 mg), ebastine (20 mg), cetirizine (10 mg) or placebo with a washout period of 5 days. Twenty‐four hours after the last dose of each treatment, histamine skin prick tests were performed (0, 0.5, 1, 2.5, 5, 10, 20, 50, 100 and 200 mg/mL), and wheal and flare responses were measured. All active treatments produced significant inhibition of the wheal responses compared to placebo (P < 0.001). Wheal response inhibition was significantly better with 20 mg of ebastine compared with 10 mg of ebastine and 10 mg of cetirizine. In a comparison to histamine concentrations required to produce a wheal surface area of 10 mm2, 20 mg of ebastine was also significantly better than ebastine 10 mg and cetirizine (P > 0.001), and 10 mg ebastine was significantly better than cetirizine (P > 0.05). Highly significant (P > 0.001) effects on the flare response were observed with each active treatment compared to placebo, with no difference between groups. The frequency of adverse events, primarily somnolence, was similar among the four treatment groups. Our results clearly indicate that ebastine, at either recommended dosage of 10 and 20 mg, and cetirizine produced significant inhibition of the histamine‐induced wheal and flare reaction compared to placebo for up to 24 h. A superior efficacy of 20 mg of ebastine is observed compared with 10 mg of ebastine and 10 mg of cetirizine on the skin wheal response 24 h after the last dose of a 6‐day‐long treatment. This study clearly proves ebastine to be an effective, truly once‐daily antihistamine.
Pharmacokinetics of cyclophosphamide (CP) and 4‐OH‐CP/aldophosphamide in systemic vasculitis
Authors: Belfayol‐Pisanté Laurence , Guillevin Loic , Tod Michel , Fauvelle Francis
Published: August 2009

Abstract—Cyclophosphamide given in association with corticosteroids has markedly improved the prognosis of systemic vasculitis. Little information has been reported on cyclophosphamide pharmacokinetics in these diseases and data evaluating its metabolite, 4‐hydroxy‐cyclophosphamide/aldophosphamide, pharmacokinetics and concentrations are lacking. Cyclophosphamide was administered as a 1‐h intravenous infusion every 3 weeks for six cycles to ten vasculitis patients. Serum cyclophosphamide and 4‐hydroxycyclophosphamide/aldophosphamide concentrations were assayed on the first cycle of the treatment by reversed‐phase high‐pressure liquid chromatography with ultraviolet detection. The mean (± SD) 4‐hydroxycyclophosphamide/aldophosphamide and cyclophosphamide areas under the serum concentration‐time curves were, respectively, 1.86 ± 1.12 and 154.1 ± 62.7 mg/L,h with a ratio of 1.30 ± 0.76%. The mean maximum serum 4‐hydroxycyclophosphamide/aldophosphamide was reached 2.3 h after cyclophosphamide administration. The mean (± SD) cyclophosphamide and 4‐hydroxycyclophosphamide/aldophosphamide half‐lives were, respectively, 5.5 ± 3.1 and 7.6 ± 2.3 h. The results are consistent with those obtained for cancer patients, in spite of a wide interpatient variability of concentrations and pharmacokinetic parameters.
Long‐lasting cyclic guanosine‐3‘,5’ ‐monophosphate accumulation in the medium of cultured smooth muscle cells from atherosclerotic rabbit aortas in response to exogenous or endogenous nitric oxide
Authors: Rupin Alain , Behr‐Roussel Delphine , Verbeuren Tony J.
Published: August 2009

Abstract—Although atherosclerosis causes a marked inhibition of the endothelium‐dependent vasorelaxation it also leads to expression of inducible nitric oxide synthase (iNOS), accompanied by an increase in cyclic GMP content, in the arterial wall. The aim of our present study was to evaluate the influence of atherosclerosis on the soluble guanylyl cyclase pathway in viable cultured smooth muscle cells (SMC) from rabbit atherosclerotic rabbit aortas (atherosclerotic SMC) and from control rabbit aortas (control SMC). In response to 100 μM sodium nitroprusside (SNP), the intracellular production of cyclic GMP was similar in both types of cells, reaching a maximum after 5 min of incubation. In the culture medium, SNP evokes an increased cyclic GMP concentration lasting 6 h in control SMC and 24 h in atherosclerotic SMC. Interleukin‐1 β (100 IU/mL), which induces iNOS in SMC from both control and atherosclerotic aortas causes accumulation of cyclic GMP in the extracellular medium between 3 and 6 h for control SMC and between 3 and 24 h with atherosclerotic SMC. These results demonstrate a long‐lasting egression of cyclic GMP in the extracellular medium of cultured SMC from rabbit aortas in response to endogenous or exogenous NO. Since this egression of cyclic GMP lasts longer in atherosclerotic than in control SMC. we suggest that atherosclerosis dysregulates the long‐term soluble guanylyl cyclase response to NO in SMC.
KR 31372, a benzopyran derivative, inhibits oxidized LDL‐stimulated proliferation and migration of vascular smooth muscle cells
Authors: Kim Hyun Hee , Ha Hun Joo , Kim Sun‐Ok , Kim Soo‐Kyung , Yoo Sung‐Eun , Hong Ki Whan
Published: August 2009

Abstract— KR 31372 is a benzopyran derivative. Both [3H]thymidine incorporation and migrations (chemotactic and wound‐edge) of cultured smooth muscle cells (SMCs) were greatly stimulated by oxidized low‐density lipoprotein (LDL). These effects were significantly suppressed by KR 31372 (10−7‐ 10−6M) and PDGF‐BB antibody (10−8‐ 10−6M). Preincubation with KR 31372 led to a decrease in the synthesis of PDGF‐BB‐like immunoreactivity (PDGF‐BB‐LI) that had been stimulated by oxidized LDL. Otherwise, KR 31372 and probucol strongly inhibited the production of thiobarbituric acid reactive substances (TBARS) caused by the incubation of LDL with Cu2+ion, and significantly reduced the intracellular oxidative stress when stimulated with H2O2. Taken together, it is suggested that KR 31372 may inhibit the oxidized LDL‐stimulated syntheses of DNA and PDGF‐BB, and migration of the SMCs, in part, via the antioxidant activity.
Lymphocyte P‐glycoprotein expression and activity before and after rifampicin in man
Authors: Becquemont Laurent , Camus Maryse , Eschwege Valérie , Barbu Véronique , Rey Elisabeth , Funck‐Brentano Christian , Jaillon Patrice
Published: August 2009

Abstract—It has recently been shown that P‐glycoprotein (P‐gp) is inducible by rifampicin in the human gut as shown in intestinal biopsies. The present study was performed in order to test the hypothesis that human peripheral lymphocytes can be used to assess such an inducibility. We also assessed inter‐ and intra‐individual variability of P‐gp expression and activity in peripheral lymphocytes. Blood samples from 13 healthy volunteers were collected 1.7, 14 and 19 days after inclusion. Rifampicin treatment (600 mg/day) was administered from clay 15 to day 18. Lymphocyte P‐gp expression was measured at the messenger RNA level by semi‐quantitative RT‐PCR and at the protein level by immunostaining flow cytometry. P‐gp activity was determined by flow cytometry with rhodamine 123 efflux. Cytochrome P4503A4 (CYP3A4) inducibility was measured by comparing the urinary metabolic ratio of 6β‐hydroxycortisol/cortisol on day 14 and 19. Lymphocyte P‐gp expression and activity was not induced by rifampicin, while it increased CYP3A4 activity from 5.0 ± 4.0 to 22.9 ± 16.6 (P < 0.001). There was a 3–4‐fold inter‐individual variability and a 3–44% intra‐individual variability of lymphocyte P‐gp expression and activity. Peripheral lymphocytes are not an appropriate material to assess P‐gp inducibility in humans. P‐gp shows significant inter‐ and intra‐individual variability in human lymphocytes.
Angiotensin II type 1 receptor antagonist versus angiotensin I‐converting enzyme inhibitor in experimental renal diseases
Authors: Jover Bernard , Demeilliers Bénédicte
Published: August 2009

Abstract— Angiotensin II has an important role in the structural and functional regulation of the cardiovascular and renal systems. Blockade of the renin‐angiotensin system can be achieved with angiotensin‐converting enzyme (ACE) inhibitors and non‐peptidic, orally active, angiotensin II type 1 receptor (ATI) antagonists. However, the question that has yet to be answered is whether ACE inhibitors and ATI receptor antagonists have similar renoprotective effects in various experimental diseases. Although many studies have assessed the role of either ACE inhibitors or ATI receptor antagonists, we have reviewed the literature comparing both types of blocker in the same experiment. In most models of hypertension or renal failure, both classes of blocker appear to have similar antihypertensive and renal profiles. In a few models, the influence of the ACE inhibitor on arterial pressure and/or renal function is more marked than that of the ATI receptor antagonist. Even though the maximum dose‐effect curve for each compound was not often carried out for the systemic haemodynamics and renal alterations, the difference between both classes of blocker, when observed, appeared to favour the participation of non‐angiotensin II or non‐ATI‐mediated mechanisms. Among them are the stimulation of prostaglandin production, kinin accumulation, nitric oxide generation and modulation of endothelin or TGFβ1 expression via direct or indirect pathways. Future experimental and probably human studies aimed at comparing angiotensin II receptor antagonists and ACE inhibitors, with respect to blood pressure and renal damage, should be designed with all these concerns in mind.
The protective effect of melatonin on cisplatin nephrotoxicity
Authors: Şener G. , Şatiroglu H. , Kabasakal L. , Arbak S. , Öner S. , Ercan F. , Keyer‐Uysal M.
Published: August 2009

Abstract—Regarding the mechanisms of cisplatin (CP) nephrotoxicity, several hypotheses have been put forward, among which oxidative stress (including depletion of glutathione and production of lipid peroxide) is noticeable. This investigation elucidates the role of the antioxidant system in CP‐induced nephrotoxicity and the nephroprotection by melatonin. Balb/c mice were injected i.p. with: 1) vehicle control; 2) a single dose of 6.5 mg/kg cisplatin, CP group; 3) melatonin in a dose of 10 mg/kg for 5 days after CP injection, CP‐M group; 4) melatonin (10 mg/kg) for 5 days before and after CP injection, M‐CP‐M group; 5) melatonin in a dose of 10 mg/kg for 5 days, M group. Mice were sacrificed 5 days after CP injection to determine blood urea nitrogen (BUN) and serum creatinine. Renal lipid peroxidation (LP) and glutathione (GSH) levels were evaluated in kidney homogenates. Cisplatin administration resulted in increased LP, BUN and serum creatinine levels and decreased GSH levels, whereas melatonin reversed these effects. Morphological kidney damage was apparent in the CP group. Mentioned degeneration was moderate in the CP‐M group, whereas morphological findings of the M‐CP‐M group implied a well preserved kidney tissue. When M was administered alone, it didn't cause any significant change in biochemical parameters. Both C and M groups exhibited similar biochemical and morphological findings in light and transmission electron microscope observation. In conclusion, the present study suggests that melatonin may be of therapeutic benefit when used with CP.
Protective effect of aminoguanidine in a murine model of pulmonary fibrosis induced by bleomycin
Authors: De Rezende Mário C. , Martinez José A.B. , Capelozzi Vera L. , Simões Manuel J. , Beppu Osvaldo S.
Published: August 2009

Abstract—Aminoguanidine is a drug known for more than a century, which has been attracting increasing interest in recent years due to the discovery of new pharmacological properties. This study investigated the effects of aminoguanidine on the fibrotic response induced by intratracheal administration of bleomycin to rats. Three groups of animals were studied: Group A (n= 19) corresponded to the control group. Group B (n= 20) received 10 IU/kg bleomycin intratracheal, and Group C (n= 12) received the same amount of bleomycin as Group B followed by 50 mg/kg/day aminoguanidine bicarbonate for 4 weeks. Aminoguanidine led to significant reductions in total hydroxyproline content of the lungs in Group C compared to Group B (Group A: 1.83 ± 0.14 mg ± Group B: 3.46 ± 0.36 mg ± Group C: 2.09 ± 0.22 mg). Morphometric collagen studies carried out on histological sections stained with Sirius red F3BA showed that aminoguanidine promoted a significant reduction of the area occupied by collagen in the axial and septal zones of the lungs (Axial region = Group A: 4.29 ± 1.31% × Group B: 19.30 ± 4.86% × Group C: 8.52 ± 1.96%; Septal region = Group A: 0.15 ± 0.06% × Group B: 0.61 ± 0.21% × Group C: 0.15 ± 0.06%). These results suggest that aminoguanidine is a potential therapeutic agent for the treatment and prevention of pulmonary fibrosis which is associated with different clinical conditions.
Effects of zinc ions on Ca2+uptake during histamine‐induced contraction in guinea‐pig taenia coli
Authors: Nasu Tetsuyuki
Published: August 2009

Abstract— The present study was undertaken to clarify the effects of zinc ions (Zn2+) on Ca2+uptake during histamine‐induced contraction in guinea‐pig taenia coli. Zn2+(0.3 mM) had smaller effect on the initial phasic response to 10−5M histamine accompanied with decreased Ca uptake at the high affinity sites, while it inhibited the tonic response by inhibiting Ca2+uptake at the low affinity sites. After the first stimulation with histamine in the presence of Zn2+, the Ca2+binding at high affinity sites was not significantly recovered in the presence of Zn2+. A second stimulation with histamine in the presence of Zn2+did not elicit any phasic response. Furthermore, after β‐escin treatment of the fibres, which leaves receptor‐coupled signal transduction including the Ca2+storage sites intact, the contraction due to 10−5M histamine was not so affected by 0.3 mM Zn2+, but, after resuspension in a solution of pCa 5, 10−5M histamine of second application did not elicit the contraction in the presence of Zn2+. These results suggested that Zn2+does not affect the histamine‐induced Ca2+release from the intracellular storage sites in taenia coli. However, when Zn2+is present, Ca2+is not supplied to the storage sites for the phasic response due to second stimulation with histamine. In addition, Zn2+reduced the tonic response to histamine mainly by inhibiting Ca2+influx through receptor‐operated and/or voltage‐dependent Ca2+channels.
Interaction between the partially insurmountable antagonist valsartan and human recombinant angiotensin II type 1 receptors
Authors: Verheijen Ilse , Fierens F.L.P. , DeBacker J.P. , Vauquelin G. , Vanderheyden P.M.L.
Published: August 2009

Abstract— The interaction between the AT1 receptor‐selective antagonist valsartan, and its human receptor, was investigated by direct radioligand binding as well as by its inhibition of angiotensin II induced inositol phosphate accumulation in CHO cells expressing human recombinant AT1 receptors. Specific binding of [3H]‐valsartan rapidly reached equilibrium at 37°C. It was saturable and occurred to a homogeneous class of sites with a KD of 0.88 ± 0.076. It was inhibited by other AT1 receptor antagonists with the same potency order as previously described for the binding of [3H]‐angiotensin II and [3H]‐candesartan to human AT1 receptors (i.e. candesartan ≥ EXP3I74 > valsartan ≅ irbesartan ≅ angiotensin II > losartan). When valsartan and angiotensin II were applied simultaneously to the CHO‐AT1 cells, the antagonist caused a rightward shift of the angiotensin II concentration‐response curve. Hence, valsartan interacts with the AT1 receptor in a manner that is competitive with angiotensin II. Pre‐incubation of the cells with 0.5, 5 and 50 nM valsartan caused an additional, concentration‐dependent, up to 55 % decline of the maximal response. The partial nature of this insurmountable inhibition by valsartan was confirmed by biphasic antagonist concentration‐inhibition curves. These data reflect the co‐existence of a fast reversible/surmountable as well as a tight binding/insurmountable valsartan‐receptor complex. In agreement, pre‐incubation of the CHO‐AT1 cells with 5 and 50 nM valsartan produced a partial inhibition of the angiotensin II induced increase of the free intracellular calcium concentration. [3H]‐Valsartan dissociated from its receptors with a half‐life of 17 min. In functional recovery experiments with valsartan‐pre‐treated cells, the angiotensin II‐mediated response was half‐maximally restored within approximately 30 min. These kinetic data suggest that the insurmountable inhibition by valsartan is related to its relatively slow dissociation from the human AT1 receptors.
Effect of lipopolysaccharide treatment on neurogenic contraction and noradrenaline release in rat arteries
Authors: Ohlmann Patrick , Martínez M. Carmen , Bucher Bernard , Andriantsitohaina Ramaroson , Muller Bernard , Schneider Francis , Stoclet Jean‐Claude
Published: August 2009

Abstract— In the present study, contractile responses and [3H]‐noradrenaline overflow evoked by electrical field stimulation were assessed, respectively, in the small mesenteric artery and in tail artery removed from rats pre‐treated with either saline or lipopolysaccharide (LPS). In small mesenteric arteries, LPS treatment did not significantly modify the contractile responses elicited by electrical stimulation, in the absence or in the presence of L‐arginine. However, in arteries removed from rats treated with LPS, L‐arginine addition produced relaxation of vessels pre‐contracted with noradrenaline. The amplification of neurogenic contraction by the nitric oxide (NO) synthase inhibitor Nω‐nitro‐L‐arginine methyl ester (L‐NAME) was similar in arteries removed from saline and LPS‐infused rats. In mesenteric arteries, LPS treatment suppressed the potentiation of the neurogenic responses by the α2‐adrenoceptor antagonist, yohimbine and by the inhibitor of neuronal uptake of noradrenaline, cocaine. In rat tail artery exposed to L‐arginine, LPS treatment produced an increase in [3H]‐nora‐drenaline overflow evoked by electrical stimulation. Altogether, these data suggest that an enhanced noradrenaline release from sympathetic nerves, probably resulting from inhibition of the modulatory effect of both prejunctional α2‐adrenoceptors and neuronal uptake mechanism, may play a role in the preservation of neurogenic response after LPS treatment despite evidence of the induction of NO synthase.
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

Many 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

The 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.
PSEUDOCODIUM MUCRONATUM, A NEW SPECIES FROM NEW CALEDONIA, AND AN ANALYSIS OF THE EVOLUTION OF CLIMATIC PREFERENCES IN THE GENUS (BRYOPSIDALES, CHLOROPHYTA)1
Authors: Payri Claude E. , Verbruggen and Heroen
Published: August 2009

A new species, Pseudocodium mucronatum, is described from the Chesterfield platform off the west coast of New Caledonia. The species differs from its congeners in having mucronate utricules. A phylogenetic analysis of rbcL and tufA sequences showed that P. mucronatum is most closely associated with P. natalense De Clerck, Coppejans et Verbruggen and P. devriesii Weber Bosse, with which it shares compressed axes, depressed apices, and plastids in the utricles and the medullar siphons. We studied the evolution of climatic and ecological preferences in the genus using an interdisciplinary approach consisting of relaxed molecular clock analysis, extraction of macroecological data from satellite imagery in a geographic information system (GIS) framework, and ancestral character state estimation. It was shown that the genus originated in tropical waters during the Early Mesozoic. Whereas the P. floridanum‐okinawense lineage remained tropical, the lineage including P. natalense, P. devriesii, and P. mucronatum gradually invaded more temperate waters during Cenozoic times. Except for P. devriesii, which occurs in shallow and intertidal habitats, all Pseudocodium species grow in deep‐water habitats, and this ecological preference appears to be ancestral.
Community blood donors' knowledge of anemia and design of a literacy‐appropriate educational intervention
Authors: Young Staci , Fink Arlene , Geiger Susan , Marbella Anne , Mast Alan E. , Schellhase Kenneth G.
Published: August 2009

BACKGROUND: The purpose of this project is to improve the health of blood donors by educating and motivating them to seek medical attention for anemia. The National Anemia Action Council, BloodCenter of Wisconsin, and the Medical College of Wisconsin formed a partnership to engage volunteer blood donors and develop an educational intervention to motivate donors with anemia to seek appropriate medical care.

STUDY DESIGN AND METHODS: Partners developed an educational pamphlet and conducted two focus groups with volunteer blood donors for feedback. Participants were recruited from volunteer donors at BloodCenter of Wisconsin found to have anemia (men age, 18 years and older with a hematocrit [Hct] level of <38%; women age 50 years and older with a Hct level of <36%) at blood screening before donation.

RESULTS: Participants (n = 25) addressed their understanding of anemia, information they received after being deferred, their reactions about the deferral, and comments on the educational material. The educational pamphlet was revised based on focus group comments.

CONCLUSION: Volunteer donors are extremely dedicated and interested in increasing their understanding of anemia and the ability to continue donation. Community members' feedback on educational material is a valuable resource to improve the literacy level of information.
Validation of a hospital‐laboratory workstation for immunohematologic methods
Authors: Schoenfeld Helge , Pretzel Karin J. , Von Heymann Christian , Neuner Bruno , Kalus Ulrich , Kiesewetter Holger , Pruss Axel
Published: August 2009

BACKGROUND: The FREELYS Nano system (Diagast) is a manual workstation for ABO/D grouping, Rh phenotyping, K typing, and antibody screening (ABS) for immunoglobulin G (IgG) antibodies only and works with the erythrocyte‐magnetized technology (EMT). The principle of EMT is based on magnetization of red blood cells and avoids centrifugation and washing steps.

STUDY DESIGN AND METHODS: A total of 304 samples were tested with our routine blood bank methods, 100 samples for ABO/D grouping, 196 samples (100 at first evaluation, 96 at second evaluation) for Rh phenotyping and K typing (PK7200, Olympus), and 108 samples for ABS (DiaMed). All samples were tested in parallel with the FREELYS Nano.

RESULTS: We found a 100% concordance between the observed (FREELYS Nano) and the expected (Olympus PK7200) results for ABO/D grouping in all 100 samples. For Rh phenotyping and K tests, in 24 of 100 samples false‐positive reactions were observed in the first evaluation by the FREELYS Nano. After changing the test kit batch for Rh phenotyping by the manufacturer, a complete concordance in Rh phenotyping and K tests was observed in a second evaluation. For ABS, the FREELYS Nano showed in 4 of 108 samples (3.7%) false‐negative reactions for IgG antibodies (two anti‐K, one anti‐E, one anti‐Cw), and one (0.9%) false‐positive reaction.

CONCLUSIONS: The FREELYS Nano is reliably suited to ABO/D grouping, Rh phenotyping, and K testing. The rate of false‐negative reactions for IgG antibodies should be reduced.
Studies of the anti–platelet factor 4/heparin immune response: adapting the enzyme‐linked immunosorbent spot assay for detection of memory B cells against complex antigens
Authors: Selleng Kathleen , Schütt Antje , Selleng Sixten , Warkentin Theodore E. , Greinacher Andreas
Published: August 2009

BACKGROUND: The anti–platelet factor 4 (PF4)/heparin immune response, which underlies heparin‐induced thrombocytopenia (HIT), has several atypical features: relatively rapid onset even without previous heparin exposure, lack of immune anamnesis, and transience of antibody production.

STUDY DESIGN AND METHODS: We modified the enzyme‐linked immunosorbent spot (ELISPOT) assay to investigate for PF4/heparin‐specific memory B cells in cardiac surgery patients, in whom the high anti‐PF4/heparin immunization rate made a prospective study feasible. The PF4‐containing antigen complexes were attached to microtiter plates via a spacer, rather than using nitrocellulose, and the final reaction enzyme substrate was added in melted agarose which, after rapid hardening, localized color development of enzyme‐tagged anti‐immunoglobulin G (IgG) probes to single PF4/heparin‐specific B cells. This modified ELISPOT assay was applied to 58 consecutive patients (testing blood from preoperative baseline and Postoperative Days 6 and 10), in which we compared detectability of PF4/heparin‐specific B cells to tetanus toxin‐specific B cells (comparator group with presumed vaccination).

RESULTS: No patient had detectable PF4/heparin‐specific memory B cells at baseline. In 2 of 30 patients (6.7%) who formed anti‐PF4/heparin IgG, PF4/heparin‐specific memory B cells (three to four spots/well) were detected by Postoperative Day 10, whereas tetanus toxin–specific memory B cells were found in 12 of 24 (50.0%) patients tested (3‐25 spots/well; p < 0.001).

CONCLUSIONS: HIT lacks a strong memory B‐cell response, perhaps explaining transience and lack of anamnesis of the anti‐PF4/heparin immune response. The technical modifications we describe for the ELISPOT assay, which permit detection of B‐cell reactions to complex antigens, could be useful for studying other immunohematologic disorders, for example, drug‐dependent thrombocytopenia and acquired hemophilia.
Simple Method to Eliminate Interference between Ventricular Assist Devices and Cardiac Rhythm Devices
Authors: BARAN DAVID A. , MARTIN TONY , BLICHARZ DONNA , CARR CANDACE , ZUCKER MARK J. , McBRIDE LAWRENCE , CAMACHO MARGARITA
Published: August 2009

Background: Report on a simple solution to allow programming of defibrillators in the presence of a Heartmate II (Thoratec Corporation, Pleasanton, CA, USA) ventricular assist device. Ventricular assist devices have become increasingly utilized for patients waiting for heart transplantation as well as those who will be maintained on a permanent support. The Heartmate II, which was recently given Food and Drug Administration approval as a bridge‐to‐transplant device, has a particular anomaly that complicates patient management. The pulse width modulator of the Heartmate II produces electromagnetic noise that interferes with the ability to interrogate and program certain defibrillators, and explantation of the defibrillator has been reported as the only viable solution.

Methods: The authors describe the use of cast‐iron pans to reduce the electromagnetic interference between St. Jude Medical's first‐generation Atlas family of defibrillators (St. Jude Medical, St. Paul, MN, USA) and the Heartmate II pump.

Results: The use of a simple shielding protocol avoids the need to remove a pre‐existing defibrillator from a patient receiving support from the Heartmate II ventricular assist device.

Conclusions: The method described herein is important as future generations of medical devices may present different types of device‐device interactions. Simple bedside methods to eliminate interference can potentially help patients who would otherwise need one or another device removed
Outpatient Electrical Cardioversion of Atrial Fibrillation: 8 Years’ Experience. Analysis of Shock‐Related Arrhythmias
Authors: MORANI GIOVANNI , CICOIRA MARIANTONIETTA , POZZANI LAURA , ANGHEBEN CARLO , ZANOTTO GABRIELE , VASSANELLI CORRADO
Published: August 2009

Background: Outpatient electrical cardioversion (EC) of atrial fibrillation is currently the standard of care. Shock‐related arrhythmias may be particularly deleterious in this setting. Preoperative identification of high‐risk patients may be very useful.

Methods: A retrospective analysis was made of 543 consecutive elective EC procedures in 457 outpatients over an 8‐year period in a university cardiological institute. The protocol included adequate anticoagulation, intravenous anesthesia, direct current shock, and a direct observation after a shock to detect procedure‐related complications. No patients were excluded due to severity of pathology or comorbidities. Clinical characteristics, energy delivered, medications, arrhythmic phenomena, and predictors of success and complications were analyzed.

Results: Of 543 ECs performed, 88.2% restored sinus rhythm, which persisted at discharge in 83.2%. No anesthesia‐related complications were detected. No thromboembolic complications were detected. Use of a biphasic cardioverter was the only predictor of success (P = 0.0001). The bradyarrhythmic complication rate was 1.5%. No ventricular arrhythmic events were detected. Atrial flutter was present in five of eight patients who developed complications versus 44 of 535 patients who had no complications (P < 0.0005), and prosthetic heart valves in four of eight complicated versus 40 of 535 uncomplicated cases (P = 0.0044). The combination of atrial flutter and prosthetic heart valve was found in four of eight complicated versus 11 of 535 uncomplicated cases (P < 0.0005).

Conclusion: Shock‐related arrhythmias are essentially bradyarrhythmias. Atrial flutter and previous cardiac surgery identify a subgroup of patients at high risk of postshock bradyarrhythmic complications.