bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decreased fracture incidence after 1 year of pamidronate treatment in children with spastic quadriplegic cerebral palsy
Authors: BACHRACH STEVEN J , KECSKEMETHY HEIDI H , HARCKE H THEODORE , HOSSAIN JOBAYER 
Published: June 2010

Aim  The aim of this study was to assess the rate of fracture before and after a 1‐year course of intravenous pamidronate in children with spastic quadriplegic cerebral palsy (CP) who had previously experienced fractures.Method  Twenty‐five children (nine males, 16 females) with quadriplegic CP in Gross Motor Function Classification System (GMFCS) level IV or V who were treated with intravenous pamidronate for approximately 1 year were identified. All participants had previously experienced at least one non‐traumatic fracture. Each received 15 doses of pamidronate over a mean of 13.6 months. Post‐treatment observation ranged from 1 to 10 years 6 months (mean 4y 1mo). The fracture rate before and after commencement of treatment was calculated using the person‐years method.Results  The participants had experienced a total of 86 fractures before treatment began, occurring over 280.6 person‐years, giving a fracture rate of 30.6% per year. During the post‐treatment observation period, totalling 107.5 person‐years, 8 of the 25 children experienced a total of 14 fractures. This fracture rate of 13.0% per year is a statistically significant decrease (p=0.02).Interpretation  Pamidronate treatment lowered the rate of fracture, and a 1‐year course appears to provide a protective effect after treatment ends. For the majority of participants, this effect lasted 4 years or longer. However, a subset of children suffered a fracture soon after the drug was discontinued. In these children, a longer course of treatment appears to have been necessary.
Do all antihypertensive drugs improve carotid intima‐media thickness? A network meta‐analysis of randomized controlled trials
Authors: Tropeano Anne‐Isabelle , Saleh Nadine , Hawajri Nasser , Macquin‐Mavier Isabelle , Maison Patrick 
Published: June 2010

AbstractThe many clinical trials investigating the effect of various antihypertensive drugs on carotid intima‐media thickness (CIMT) produced conflicting results. We used meta‐analysis to evaluate CIMT changes and network meta‐analysis to rank drugs according to the magnitude of these changes. We identified 31 randomized controlled trials listed in three databases as of January 2008. Using a random‐effects model, we found a significant CIMT decrease with antihypertensive drugs compared to placebo (−0.10 [−0.16; −0.04]). Overall effect sizes vs. placebo were significant for angiotensin‐converting enzyme (ACE) inhibitors (−0.08 [−0.14; −0.02]), and a trend was found for beta‐blockers (−0.09 [−0.19; 0.01]). The data did not allow other direct comparisons vs. placebo. Significant benefits were found for calcium‐channel blockers (CCBs) compared to both ACE inhibitors (0.37 [0.20; 0.54]), as well as for angiotensin II receptor blockers (ARBs) compared to beta‐blockers (0.42 [0.29; 0.55]). Diuretics were less efficient than CCBs (−0.09 [−0.16; −0.02]). Indirect comparisons with network meta‐analysis showed significant effects of CCBs and ARBs vs. placebo (both P < 0.05) and vs. diuretics (both P < 0.001). The CIMT decrease with ACE inhibitors and beta‐blockers was greater than with diuretics (both P < 0.05) but was not different from the placebo effect. In subgroup analyses, significant benefits occurred with lower baseline CIMT values and shorter treatment durations but were unrelated to the size of the blood pressure decrease. In conclusion, among antihypertensive drugs, CCBs and ARBs have the greatest effect on CIMT.
Effects induced by inhibitors of the phosphatidylinositol 3‐kinase/Akt and nitric oxide synthase/guanylyl cyclase pathways on the isometric contraction in rat aorta: a comparative study
Authors: López Ruth M. , Pérez Teresa , Castillo Carlos , Castillo Enrique F. 
Published: June 2010

AbstractThis work was aimed to determine whether isometric contraction in Wistar rat aorta is related to the phosphatidylinositol 3‐kinase (PI3K)/Akt‐dependent activation of endothelial nitric oxide synthase (eNOS). Basically, we hypothesized that additional increases in active tone occur after the pharmacological inhibition of a transduction pathway involved in NO synthesis or action. In intact aortic rings contracted with phenylephrine or high K+, the cumulative administration of the PI3K inhibitor, LY294002, elicited significant decreases – but not supplementary increases – in tone. In endothelium‐intact tissues, on the other hand, the Akt1/2 kinase inhibitor did not alter phenylephrine‐ and K+‐induced isometric contractions. The PI3K inhibitor wortmannin (1 × 10−7 m) produced a significant supplementary contraction only in endothelium‐intact aortic rings precontracted with phenylephrine. Higher concentrations of this inhibitor produced relaxations of phenylephrine and high K+‐constricted endothelium‐intact and endothelium‐denuded aortic rings. LY294002 and wortmannin did not cause any potentiating effect on phenylephrine‐ and angiotensin II‐induced concentration‐dependent contractile responses in endothelium‐intact tissues. In intact aortic rings contracted with phenylephrine or high K+, the addition of the NOS inhibitor, L‐NAME, or the guanylyl cyclase inhibitor, ODQ, further augmented tone in a concentration‐dependent manner, and these supplementary contractions were significantly reduced by endothelium removal. Taken together, our data suggest that the PI3K/Akt pathway is not counteracting aortic isometric contractions by activation of the eNOS. It appears, on the other hand, that the smooth muscle PI3K can stimulate contraction without activation of the protein kinase Akt in response to GPCR agonists and high K+.
Neuropharmacological effects of lipoic acid and ubiquinone on the mRNA level of interleukin‐1β and acetylcholinesterase activity in rat hippocampus after seizures
Authors: de Freitas Rivelilson M. , Gomes Katia N. , Saldanha Gláucio B. 
Published: June 2010

AbstractThe purpose of this study was to investigate the neuroprotective effects of lipoic acid and ubiquinone on interleukin‐1β (IL‐1β) mRNA levels and acetylcholinesterase (AChE) activities in rat hippocampus after pilocarpine‐induced seizures. Wistar rats were intraperitoneally administered with either 0.9% saline (icontrol group), LA (10 or 20 mg/kg, LA10 or LA20 groups), UQ (20 or 40 mg/kg, UQ20 and UQ40 groups), pilocarpine (400 mg/kg, P400 group), or co‐administration of pilocarpine with LA or UQ groups 30 min prior to LA or UQ administration. After the treatments, all groups were observed for 1 h. IL‐1β mRNA and AChE activity in rat hippocampus at 1 h after SE onset was determined. Results showed that rats pretreated with LA or UQ developed less seizures and SE more slowly and has less number than animals treated with pilocarpine alone. Reduced IL‐1β mRNA and marked AChE activities in the hippocampus were significantly higher in rats pretreated with LA or UQ in comparison with the values of the control and seized groups. Our findings strongly support the hypothesis that an increase on IL‐1β mRNA levels in hippocampus occurs during seizures induced by pilocarpine, which indicates that inflammatory process plays a crucial role in seizures pathogenic consequences. Our result also suggests that LA or UQ can exert significant neuroprotective effects, at least in part, because of the increase in the AChE activities in rat hippocampus that will be useful in the treatment of neurodegenerative diseases.
Reduced cardiac remodelling and prevention of glutathione deficiency after omega‐3 supplementation in chronic heart failure
Authors: Fang Yuehua , Favre Julie , Vercauteren Magalie , Laillet Brigitte , Remy‐Jouet Isabelle , Skiba Mohamed , Lallemand Françoise , Dehaudt Cathy , Monteil Christelle , Thuillez Christian , Mulder Paul 
Published: June 2010

Abstractn‐3 polyunsaturated fatty acids (omega‐3) supplementation is associated with reduced cardiovascular mortality and post‐infarction death. However, the impact of omega‐3 supplementation in congestive heart failure (CHF) is still unknown. This study assesses the effects of omega‐3 supplementation on left ventricular (LV) function and remodelling. We assessed, in rats with CHF induced by left coronary ligation, the effects of a 1‐week and a 12‐week supplementation with omega‐3 (450 mg/kg per day) on LV hemodynamics, function and structure. Chronic omega‐3 reduces total peripheral resistance due to an increase in cardiac output without modification of arterial pressure. Only chronic omega‐3 reduces LV end‐diastolic pressure and LV relaxation constant. Moreover, chronic omega‐3 decreases LV systolic and diastolic diameters, LV weight and collagen density. Acute and chronic omega‐3 increase LV γ‐glutamyl‐cysteine synthetase and oppose glutathione deficiency resulting in a reduction of myocardial oxidized glutathione. In experimental CHF, long‐term omega‐3 supplementation improves LV hemodynamics and function and prevents LV remodelling and glutathione deficiency. The latter might be one of the mechanisms involved, but whether other mechanism, independent of myocardial redox ‘status’, such as reduced inflammation, are implicated remains to be confirmed.
Inhibition of the diclofenac‐induced cyclooxygenase‐2 activity by paracetamol in cultured macrophages is not related to the intracellular lipid hydroperoxide tone
Authors: Ayoub Samir S. , Joshi Amrish , Chol Mary , Gilroy Derek W. , Seed Michael P. 
Published: June 2010

AbstractParacetamol, a weak inhibitor of cyclooxygenase COX‐1 and COX‐2 activities, has been reported to inhibit the activity of COX‐2 induced by diclofenac in J774.2 macrophage cell line. The lack of inhibition of COX‐2 by paracetamol in inflamed tissues and thereby the lack of anti‐inflammatory activity has been attributed to high lipid hydroperoxide (LHP) tone. In this study, we demonstrate that the inhibition of the diclofenac‐induced COX‐2 activity in J774.2 cells by paracetamol is not related to the intracellular LHP tone as paracetamol inhibited this activity in the absence and presence of T‐butyl hydroperoxide, which is an LHP donor, to the same extents. In fact, treatment of the cells with diclofenac resulted in an increase in the LHP tone. Stimulation of the cells with lipopolysaccharide (LPS) results in the induction of a COX‐2 activity, which was not inhibited by paracetamol. This represents the classical induction pathway for COX‐2. LPS stimulation did not alter the LHP tone. These results suggest that the enzymatic activity of the diclofenac‐induced COX‐2 protein does not depend on the supply of hydroperoxides to its peroxidase active site.
Are Lower Response Rates Hazardous to Your Health Survey? An Analysis of Three State Telephone Health Surveys
Authors: Davern Michael , McAlpine Donna , Beebe Timothy J. , Ziegenfuss Jeanette , Rockwood Todd , Call Kathleen Thiede 
Published: June 2010

Objective. To examine the impact of response rate variation on survey estimates and costs in three health telephone surveys.Data Source. Three telephone surveys of noninstitutionalized adults in Minnesota and Oklahoma conducted from 2003 to 2005.Study Design. We examine differences in demographics and health measures by number of call attempts made before completion of the survey or whether the household initially refused to participate. We compare the point estimates we actually obtained with those we would have obtained with a less aggressive protocol and subsequent lower response rate. We also simulate what the effective sample sizes would have been if less aggressive protocols were followed.Principal Findings. Unweighted bivariate analyses reveal many differences between early completers and those requiring more contacts and between those who initially refused to participate and those who did not. However, after making standard poststratification adjustments, no statistically significant differences were observed in the key health variables we examined between the early responders and the estimates derived from the full reporting sample.Conclusions. Our findings demonstrate that for the surveys we examined, larger effective sample sizes (i.e., more statistical power) could have been achieved with the same amount of funding using less aggressive calling protocols. For some studies, money spent on aggressively pursuing high response rates could be better used to increase statistical power and/or to directly examine nonresponse bias.
The 5‐lipoxygenase inhibitor, zileuton, suppresses prostaglandin biosynthesis by inhibition of arachidonic acid release in macrophages
Authors: Rossi A , Pergola C , Koeberle A , Hoffmann M , Dehm F , Bramanti P , Cuzzocrea S , Werz O , Sautebin L 
Published: June 2010

BACKGROUND AND PURPOSEZileuton is the only 5‐lipoxygenase (5‐LOX) inhibitor marketed as a treatment for asthma, and is often utilized as a selective tool to evaluate the role of 5‐LOX and leukotrienes. The aim of this study was to investigate the effect of zileuton on prostaglandin (PG) productionin vitroandin vivo.EXPERIMENTAL APPROACHPeritoneal macrophages activated with lipopolysaccharide (LPS)/interferon γ (LPS/IFNγ), J774 macrophages and human whole blood stimulated with LPS were used asin vitromodels and rat carrageenan‐induced pleurisy as anin vivomodel.KEY RESULTSZileuton suppressed PG biosynthesis by interference with arachidonic acid (AA) release in macrophages. We found that zileuton significantly reduced PGE2 and 6‐keto prostaglandin F1α (PGF1α) levels in activated mouse peritoneal macrophages and in J774 macrophages. This effect was not related to 5‐LOX inhibition, because it was also observed in macrophages from 5‐LOX knockout mice. Notably, zileuton inhibited PGE2 production in LPS‐stimulated human whole blood and suppressed PGE2 and 6‐keto PGF1α pleural levels in rat carrageenan‐induced pleurisy. Interestingly, zileuton failed to inhibit the activity of microsomal PGE2 synthase1 and of cyclooxygenase (COX)‐2 and did not affect COX‐2 expression. However, zileuton significantly decreased AA release in macrophages accompanied by inhibition of phospholipase A2 translocation to cellular membranes.CONCLUSIONS AND IMPLICATIONZileuton inhibited PG production by interfering at the level of AA release. Its mechanism of action, as well as its use as a pharmacological tool, in experimental models of inflammation should be reassessed.
Flavocoxid, a dual inhibitor of cyclooxygenase‐2 and 5‐lipoxygenase, reduces pancreatic damage in an experimental model of acute pancreatitis
Authors: Polito F , Bitto A , Irrera N , Squadrito F , Fazzari C , Minutoli L , Altavilla D 
Published: June 2010

BACKGROUND AND PURPOSE Acute pancreatitis is an autodigestive process resulting in acute inflammation of the pancreas. Accumulating evidence indicates the essential contribution of cyclooxygenase (COX)‐2 and 5‐lipoxygenase (5‐LOX) to acute pancreatitis. We studied the effects of flavocoxid, a plant‐derived dual inhibitor of COX‐2 and 5‐LOX, in a model of caerulein (CER)‐induced acute pancreatitis.EXPERIMENTAL APPROACH Rats were given CER (80 µg·kg−1 for each of four injections at hourly intervals) or vehicle (Sham‐CER). Animals were then randomized to receive flavocoxid (20 mg·kg−1 i.p.) or vehicle, 30 min after the first CER injection. Two hours after the last CER injection, we evaluated damage to the pancreas by histological methods; serum levels of amylase, lipase, leukotriene (LT)B4 and prostaglandin (PG)E2; pancreatic expression of COX‐2 and 5‐LOX and tumour necrosis factor‐α (TNF‐α) gene expression by real‐time polymerase chain reaction.KEY RESULTS Caerulein induced inflammatory changes in the pancreas and raised values of the other variables measured. In CER‐treated animals, but not in those given saline, flavocoxid inhibited COX‐2 and 5‐LOX expression, reduced serum levels of lipase and amylase and the degree of pancreatic oedema. Treatment with flavocoxid blunted the increased pancreatic TNF‐α mRNA expression, serum leukotriene B4 and prostaglandin E2 levels, and protected against histological damage in terms of vacuolization and leukocyte infiltration.CONCLUSIONS AND IMPLICATIONS Our results confirm the key role of both COX‐2 and 5‐LOX in the inflammatory response to acute pancreatitis. Flavocoxid may provide a potential therapeutic approach to the treatment of patients at high risk of developing this life‐threatening condition.
The Electro‐Mechanical window: a risk marker for Torsade de Pointes in a canine model of drug induced arrhythmias
Authors: van der Linde HJ , Van Deuren B , Somers Y , Loenders B , Towart R , Gallacher DJ 
Published: June 2010

BACKGROUND AND PURPOSE In cardiovascular pharmacology, electrical and mechanical events can be distinguished, and the phrase ‘electro‐mechanical window’ (EMw) describes the temporal difference between these events. We studied whether changes in EMw have potential predictive value for the occurrence of arrhythmias in fentanyl/etomidate‐anaesthetized beagle (FEAB) dogs.EXPERIMENTAL APPROACH The EMw was calculated as differences between the QT interval and QLVPend in FEAB dogs during atrial pacing, treatment with isoprenaline or atropine, body temperature changes and induction of Torsade de Pointes (TdP) in an LQT1 model.KEY RESULTS The electrical systole (QT interval) was shorter than the duration of the mechanical event (QLVPend), providing a positive EMw. Atrial pacing, atropine or body temperature changes had no major effects on EMw, despite large changes in QT duration. However, β‐adrenoceptor stimulation (with isoprenaline) decreased the EMw (from 90 to 5 ms) and in combination with HMR1556, a blocker of the slowly activating potassium current (IKs), induced a large negative EMw (–109 ms) and TdP. Prevention of TdP by atenolol or verapamil was associated with a less negative EMw (–23 to –16 ms). Mexiletine, a poorly effective long QT treatment, did not affect the EMw or prevent TdP induction.CONCLUSIONS AND IMPLICATIONS The EMw is a marker, other than QT prolongation, of TdP risk in the FEAB model. Therefore, we suggest examining the EMw as a risk marker in cardiovascular safety studies and as a potential biomarker to improve clinical management of long QT syndrome patients, especially in patients with borderline QT prolongation.LINKED ARTICLE This article is commented on by Vargas, pp. 1441–1443 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476‐5381.2010.00980.x
Shade Coffee in Biological Corridors: Potential Results at the Landscape Level in El Salvador
Authors: Romanoff Steven 
Published: June 2010

AbstractMight the cost of certifying coffee farms limit the capacity of certification to cover a landscape and protect biodiversity? Gobbi simulated financial viability and Taylor and colleagues asked, “Does the premium pay off?” but there is little empirical evidence. In two years, a project in western El Salvador developed such data as farmers prepared for certification under Rainforest Alliance norms or verification for Starbuck's Coffee. On 45 sample farms, major investments were shade trees, soil/water conservation, and water supply for workers. At the aggregated or landscape level, investment on‐farm cost US$77 per hectare of coffee. Further, it cost US$53 per hectare for audits and technical assistance, and more than US$30 for increased operating expenses. (Average figures per hectare across farms differed considerably: US$111 per hectare.) Returns in the first year of certification were price bonuses for certified coffee (US$191 per hectare at the aggregate level) and part of unexpectedly large production increases (US$265 per hectare, aggregate), totaling US$456 per hectare. (Average per hectare across farms gross benefits differed: US$734 per hectare.) More than half of the farms did very well with certification, even in the first year. A good market, low baseline productivity, unused productive capacity, and institutional support for extension and certification contributed. Bottom line: 300 farms were certified on 11,000 hectares covering one‐third of a major coffee landscape and substantial aggregate investments in conservation. Comparative or follow‐on data are needed for perspective on these results, to show if benefits were sustained, and to allow financial calculations.
Bone reaction adjacent to microplasma‐sprayed CaP‐coated oral implants subjected to occlusal load, an experimental study in the dog. Part I: short‐term results
Authors: Junker R. , Manders P. J. D. , Wolke J. , Borisov Y. , Jansen J. A. 
Published: June 2010

AbstractBackground: A new microplasma spraying equipment (MSE) to deposit calcium phosphate ceramic (CaP) coatings onto titanium substrates has been developed. With this system, it is possible to spray fine particles and to apply textured hydroxylapatite coatings onto titanium surfaces. Moreover, due to the low heat power of the microplasma jet, overheating of the powder particles as well as excessive local overheating of the substrate is diminished. Furthermore, because of the small laminar plasma jet, it is possible to achieve high spray efficiency in the case of spraying for dental implants. Also, the low level of noise (25–50 dB) and hardly any dust makes it possible to operate MSE under conditions of normal workrooms.Objective: The aim was to investigate, in a mandibular dog model, bone biological properties and the occlusal loading effects of titanium implants provided with newly developed microplasma‐sprayed CaP coatings.Material and methods: For histomorphometrical evaluation, 48 screw‐type titanium implants were inserted into the mandibles of six adult beagle dogs. The implants were either acid etched without additional coating, coated with a conventionally plasma‐sprayed CaP ceramic, coated with a microplasma‐sprayed CaP ceramic or with a microplasma‐sprayed coating at the apical part only. To assess the effect of occlusal loading, a split‐mouth design was used. Six weeks after implantation, the implants in one half of the mandible of each dog were functionally loaded, while the contra lateral implants served as control. Six weeks after loading, the animals were sacrificed and bone‐to‐implant contact as well as the amount of bone around the implants were assessed.Results: Irrespective of surface and functional load, no statistically significant differences (P>0.05) were found either for bone‐to‐implant contact or for the amount of bone between the various implant surfaces. On the other hand, functional loading of the non‐coated implants was associated with a tendency towards crestal bone loss.Conclusion: Within the limits of the experiment, we conclude that functional loading of MPS CaP coatings induces a favorable bone response, and furthermore, that the bone response, irrespective of the loading condition, does not differ from conventional plasma‐sprayed CaP coatings. To cite this article:
Junker R, Manders PJD, Wolke J, Borisov Y, Jansen JA. Bone reaction adjacent to microplasma‐sprayed CaP‐coated oral implants subjected to occlusal load, an experimental study in the dog. Part I: Short‐term results. Clin. Oral Impl. Res. 21, 2010; 1251–1263. doi: 10.1111/j.1600‐0501.2010.01940.x