bluuebunny/crossref_metadata_2025 huggingface dataset:
Rod-through-plate fixation of canine diaphyseal fractures
Authors: Andrianov V. , Tralman G. , Hõim R. , Haviko T. , Lenzner A. , Pääsuke M. , Arend A. , Aunapuu M.
Published: July 2007

Efficacy of the rod-through-plate fixation for fracture repair was evaluated in six clinical cases of canine long bone fractures. This fixation incorporates principles of intramedullary and extramedullary osteosynthesis for transverse and short oblique fractures of long tubular bones. The plate-through-rod device is comprised of one pair of curved rods, a connecting plate and two bone screws. The connecting plate has both a hole and a channel on each end. Curved rods have a long curved part and a straight part with a hole in it for screw fixation. All components are made up of medical stainless steel. Clinical and radiographical examinations were performed from week seven to18 months after the operation. Functional abnormalities were not observed at this period in five patients and all fractures were healed. In one patient screw stripping in the proximal fragment of the femur was detected radiologically and minimal implant dislocation was noted at seven weeks after the initial repair. The rod-through-plate fixation method gives strong fixation of bone fragments with minimal traumatization of soft tissue during the operation. The design of the rod-through-plate is intended to reduce pressure of the plate on the cortex in the area of the fracture, whereas the dynamic fixation provided by the intramedullary rods may allow micromotion, thus stimulating callus formation and avoiding implant- induced osteoporosis. Clinical relevance: The rod-through-plate fixator has a simple construction and its use expands the treatment possibilities for diaphyseal fractures of long bones.
A mechanical evaluation of pre-tapped and self-tapped screws in small bones
Authors: Bell J. C. , Ness M. G.
Published: July 2007

The purpose of this study was to compare the holding powers of 2.7 mm pre-tapped and self-tapped screws placed closely together and tightened in small bones. Pairs of metatarsals were collected from healthy, skeletally mature Greyhounds and part of a 2.7 mm dynamic compression plate was fixed to the dorsal surface of each bone using three 2.7 mm screws. Identical screws were used throughout but only one of each pair of bones had threads pre-cut using a tap prior to insertion. All of the screws were tightened before the constructs were mounted in a materials testing machine and the centrally placed screw was loaded incrementally until failure. Load-deformation curves were plotted and yield point, ultimate load to failure, stiffness and energy prior to yield point were measured. Mean values were recorded for each parameter and Student's T-test was used to test the null hypothesis that there is no difference in holding power between pre-tapped and self-tapped screws. Significant mechanical differences were not found between pre-tapped and self-tapped screws placed closely together and tightened into small bones. Self-tapped screws can be considered for use in small animal surgery even when multiple screws are to be placed closely together in relatively small pieces of bone.
Augmentation of the transverse acetabular ligament in canine caudoventral hip luxation
Authors: Montavon P. M. , Venzin C.
Published: July 2007

Open surgical fixation was performed on four hip joints in three dogs who were suffering from caudoventral hip luxations for which closed reduction had previously failed. Stabilization of the joint was achieved with a ventral coxofemoral approach, which augmented the function of the transverse acetabular ligament using a sling implant through a bone tunnel (n=1), a sling implant around two pelvic screws (n=1), or an internal fixator plate (n=2). Transverse acetabular ligament augmentation resulted in successful joint stabilization in all cases, and should be considered for the surgical reduction of caudoventral hip luxations in dogs. The use of an internal fixator plate, while preserving soft-tissue blood supply and resulting in minimal to no long-term arthritic changes, may provide an optimal outcome.
Radiographic and clinical features of carpal varus associated with chronic sprain of the lateral collateral ligament complex in 10 dogs
Authors: Hamilton M. H. , Pratt J. N. J. , Langley-Hobbs S. J.
Published: July 2007

Lameness associated with carpal varus deformity was recognised in 10 dogs, eight of which were Dobermann Pinschers. The dogs had a mean age of seven years and nine months. Carpal varus was usually bilateral with concurrent carpal hyperflexion and pronation. Carpal varus was present prior to the onset of lameness in four cases. With stress radiography the median angle of varus deviation in all carpi was 14.6°, and an increase in the size of the ulnar /ulnar carpal bone joint space was seen in six of the seven dogs. Radiographic changes included: enthesophyte formation at the proximolateral aspect of metacarpal V, periarticular soft tissue swelling, especially lateral, bone proliferation at the carpometacarpal joint I and enthesophyte formation at metacarpophalangeal joint V. Four dogs were admitted for problems other than carpal varus and lameness was not treated. Five dogs were treated with nonsteroidal anti-inflammatory drugs, but lameness was not completely resolved and became exacerbated with exercise. One dog was successfully treated by pancarpal arthrodesis.
Fixation of humeral intercondylar fractures using a lateral plate in 14 dogs supported by finite element analysis of repair
Authors: Comiskey D. P. , Mac Donald B. , Garvan C. B. , Mc Cartney W. T.
Published: July 2007

Fourteen Spaniels that presented with an intercondylar fracture of the distal humerus were managed using a lateral plate and an additional pin in twelve cases. Fixation of the fracture was achieved using a plate applied laterally which incorporated the transcondylar lag screw in the most distal hole. Of the 14 cases, two had poor results, one of which was a bilateral case, whilst the remaining 12 cases had good or very good results with only occasional stiffness or lameness. Finite element (FE) modelling of a distal humerus was generated, and loading of fracture repairs using a lateral plate and caudal plate was completed in a comparative study to determine which fixation method resisted micro-motion most effectively. Finite element analysis revealed that the lateral plate fixation provided significantly more resistance to micro movement at the fracture site that the caudal plate fixation, with 40% more micro-motion in the latter.
Mechanoreceptors in the medial and lateral glenohumeral ligaments of the canine shoulder joint
Authors: Spadari A. , Bombardi C. , Casadio Tozzi A. , De Sordi N. , Lucchi M. L. , Grandis A.
Published: July 2007

In order to have a better understanding of the role of ligaments in canine shoulder joint stability, the presence of mechanoreceptors in the medial (MGHL) and lateral (LGHL) glenohumeral ligaments was detected by means of a modified gold chloride stain. Three morphologically distinct mechanoreceptors were identified: Ruffini receptors (type I endings), Pacinian corpuscles (type II endings) and Golgi tendon organ-like receptors (type III endings). These receptors are mainly localized at each end of the ligaments and are prevalently in their glenoid portion. In particular, in the MGHL the highest density was at the cranial arm of the insertion into the scapula. The variety of mechanoreceptors in canine shoulder ligaments might indicate an afferent function in providing the CNS with joint proprioceptive information. Therefore, besides acting as passive mechanical stabilizers, the MGHL and the LGHL may serve as sensory structures, contributing actively to joint stability. Ligamentous injuries which occur in shoulders not only affect mechanical restraint but also alter the proprioceptive input to the CNS by means of disruption of the mechanoreceptors.
Force plate gait analysis at the walk and trot in dogs with low-grade hindlimb lameness
Authors: Imhof J. , Kaestner S. , Montavon P. M. , Voss K.
Published: July 2007

Objective: To evaluate the accuracy of force plate gait analysis at the walk and trot in dogs with low-grade hindlimb lameness. Material and methods: Nineteen healthy dogs and 41 dogs with low-grade unilateral hindlimb lameness due to stifle or hip joint problems were walked and trotted over a force plate. Peak vertical forces (PVF) were recorded, and a symmetry index (SI) was calculated from the PVF of the hindlimbs. ‘Cut-off’ values were determined from the SI of the normal dogs. These cut-off values were used to discriminate lame dogs from normal ones. Sensitivity and specificity were evaluated for measurements at walk and trot, and the Cohen’s Kappa coefficient (k) was used to determine the agreement between clinical lameness and force plate measurements, and between force plate results at walk and trot. Receiver Operating Characteristics (ROC) curve were plotted for both gaits to evaluate accuracy. Results: The sensitivity of the measurements at walk was 0.63, and specifity was 0.95. The sensitivity of the measurements at trot was 0.90, and specificity was 1.0. Moderate agreement was found between force plate measurements at walk and trot, and between clinical gait assessment and force plate measurements at walk. Good agreement was found between clinical gait assessment and measurements at trot. ROC analyses revealed the trot (94.7% [91.7%; 97.7%]) to be the more accurate test than the walk (85.0% [80.1%; 89.9%]). Conclusion: The trotting gait was more sensitive and accurate than the walking gait for the differentiation of dogs with a low-grade hindlimb lameness from normal ones using force plate gait analysis.
Management of traumatic urethral rupture in 11 cats using primary alignment with a urethral catheter
Authors: Sarrau S. , Autefage A. , Meige F.
Published: July 2007

Objective: To assess the management of traumatic urethral ruptures using a systematic attempt at urethral catheterisation. Methods: Eleven cats that had been diagnosed with a traumatic urethral rupture over a five- year period were included in this study. Rupture was assessed by positive-contrast retrograde urethrography. An attempt was made to manage these ruptures by placing an indwelling urethral catheter. Results: The placement of an indwelling urethral catheter, could be performed in 10 out of 11 cats, which indicated a partial rupture. In one cat, catheterisation was not possible because of complete urethral rupture. A urethral catheter was placed into the urinary bladder via the urethra in five animals. In the other five animals, urethral catheterization required cystotomyusing a modified ‘inside to outside’ technique. Urethral catheter removal occurred between five and 14 days after placement. Urethral healing was accomplished in all cases of catheterisation with a good outcome in eight of the 10 cats. Two cats showed clinical signs related to stricture formation during the follow-up period (seven to 72 months). Retrograde urethrography provided a definitive diagnosis of partial rupture in only six of the 10 cases of partial rupture. Clinical significance: Results suggested that primary alignment with the placement of a urethral catheter should be attempted for the management of traumatic urethral ruptures in cats. Gentle urethral catheterisation seems to be an effective procedure for diagnosing and dealing with partial urethral rupture in cats. Clinical stricture formation can occur, but the risk does not seem to be high. Further studies are warranted in order to define the ideal duration for maintenance of an indwelling urethral catheter in cases of traumatic partial urethral rupture.
The role of bone morphogenetic proteins in articular cartilage development, homeostasis and repair
Authors: Oshin A. O. , Stewart M. C.
Published: July 2007

Bone morphogenetic proteins (BMPs) are members of the TGF-β superfamily of secreted ligands. BMPs regulate a diverse range of developmental processes during embryogenesis and postnatal development, and control the differentiation of several musculoskeletal tissues including bone, cartilage, tendon and ligaments. The ability of BMPs to modulate the phenotype of cells in these tissue lineages suggests that these factors could be valuable for musculoskeletal tissue regeneration. In fact, BMPs-2 and -7 are already in clinical use for bone regeneration. This review addresses the signaling mechanisms by which BMPs regulate cellular processes, the role of BMPs in articular cartilage development and joint formation, and the data that supports the use of BMPs for in vitro phenotypic support of articular chondrocyte cultures, chondrogenic differentiation of mesenchymal stem cells (MSCs) and articular cartilage repair. Given the documented importance of BMP activity for normal joint formation, articular cartilage development and maintenance, the chondrogenic activity of BMPs when applied to MSC cultures and the encouraging outcomes of several in vivo cartilage repair studies, BMP therapies hold considerable promise for effective cartilage repair and/or regeneration. Future advances in the control of BMP elution from biocompatible matrices and prolonged, dose-controlled BMP expression by genetically engineered cells should substantially improve cartilage repair strategies using BMPs and similar chondro-protective proteins.
Intrauterine Exposure to Maternal Atherosclerotic Risk Factors Increases the Susceptibility to Atherosclerosis in Adult Life
Authors: Alkemade Fanneke E. , Gittenberger-de Groot Adriana C. , Schiel Anja E. , VanMunsteren J. Conny , Hogers Bianca , van Vliet Leontien S. J. , Poelmann Robert E. , Havekes Louis M. , Willems van Dijk Ko , DeRuiter Marco C.
Published: July 2007

Objective—

Maternal hypercholesterolemia is associated with a higher incidence and faster progression of atherosclerotic lesions in neonatal offspring. We aimed to determine whether an in utero environment exposing a fetus to maternal hypercholesterolemia and associated risk factors can prime the murine vessel wall to accelerated development of cardiovascular disease in adult life.

Methods and Results—

To investigate the epigenetic effect in utero, we generated genetically identical heterozygous apolipoprotein E–deficient progeny from mothers with a wild-type or apolipoprotein E–deficient background. A significant increase in loss of endothelial cell volume was observed in the carotid arteries of fetuses of apolipoprotein E–deficient mothers, but fatty streak formation was absent. Spontaneous atherosclerosis development was absent in the aorta and carotid arteries in adult life. We unilaterally placed a constrictive collar around the carotid artery to induce lesion formation. In offspring from apolipoprotein E–deficient mothers, collar placement resulted in severe neointima formation in 9 of 10 mice analyzed compared with only minor lesion volume (2 of 10) in the progeny of wild-type mothers.

Conclusions—

We conclude that the susceptibility to neointima formation of morphologically normal adult arteries is already imprinted during prenatal development and manifests itself in the presence of additional atherogenic risk factors in adult life. Future research will concentrate on the mechanisms involved in this priming process, as well as on prevention strategies.
Platelet-Derived Growth Factor Receptor-β Constitutive Activity Promotes Angiogenesis In Vivo and In Vitro
Authors: Magnusson Peetra U. , Looman Camilla , Åhgren Aive , Wu Yan , Claesson-Welsh Lena , Heuchel Rainer L.
Published: July 2007

Objective—

Knockout studies have demonstrated crucial roles for the platelet-derived growth factor-B and its cognate receptor, platelet-derived growth factor receptor-β (PDGFR-β), in blood vessel maturation, that is, the coverage of newly formed vessels with mural cells/pericytes. This study describes the consequences of a constitutively activating mutation of the PDGFR-β (
Pdgfrb

D849V

) introduced into embryonic stem cells with respect to vasculogenesis/angiogenesis in vitro and in vivo.

Methods and Results—

Embryonic stem cells were induced to either form teratomas in vivo or embryoid bodies, an in vitro model for mouse embryogenesis. Western blotting studies on embryoid bodies showed that expression of a single allele of the mutant
Pdgfrb
led to increased levels of PDGFR-β tyrosine phosphorylation and augmented downstream signal transduction. This was accompanied by enhanced vascular development, followed by exaggerated angiogenic sprouting with abundant pericyte coating as shown by immunohistochemistry/immunofluorescence.
Pdgfrb

D849V
/+

embryoid bodies were characterized by increased expression of vascular endothelial growth factor (VEGF)-A and VEGF receptor-2; neutralizing antibodies against VEGF-A/VEGF receptor-2 blocked vasculogenesis and angiogenesis in mutant embryoid bodies. Moreover,
Pdgfrb

D849V
/+

embryonic stem cell–derived teratomas in nude mice were more densely vascularized than wild-type teratomas.

Conclusion—

Increased PDGFR-β kinase activity is associated with elevated expression of VEGF-A and VEGF receptor-2, acting directly on endothelial cells and resulting in increased vessel formation.
Genetic Susceptibility to Peripheral Arterial Disease: A Dark Corner in Vascular Biology
Authors: Knowles Joshua W. , Assimes Themistocles L. , Li Jun , Quertermous Thomas , Cooke John P.
Published: July 2007

Peripheral arterial disease (PAD) is characterized by reduced blood flow to the limbs, usually as a consequence of atherosclerosis, and affects ≈12 million Americans. It is a common cause of cardiovascular morbidity and an independent predictor of cardiovascular mortality. Similar to other atherosclerotic diseases, such as coronary artery disease, PAD is the result of the complex interplay between injurious environmental stimuli and genetic predisposing factors of the host. Genetic susceptibility to PAD is likely contributed by sequence variants in multiple genes, each with modest effects. Although many of these variants probably alter susceptibility both to PAD and to coronary artery disease, it is likely that there exists a set of variants specifically to alter susceptibility to PAD. Despite the prevalence of PAD and its high societal burden, relatively little is known about such genetic variants. This review summarizes our limited present knowledge and gives an overview of recent, more powerful approaches to elucidating the genetic basis of PAD. We discuss the advantages and limitations of genetic studies and highlight the need for collaborative networks of PAD investigators for shedding light on this dark corner of vascular biology.
Ischemia Is Not Required for Arteriogenesis in Zebrafish Embryos
Authors: Gray Caroline , Packham Ian M. , Wurmser François , Eastley Nicholas C. , Hellewell Paul G. , Ingham Philip W. , Crossman David C. , Chico Timothy J.A.
Published: July 2007

Objective—

The role of ischemia in collateral vessel development (arteriogenesis) is a contentious issue that cannot be addressed using mammalian models. To investigate this, we developed models of arteriogenesis using the zebrafish embryo, which gains sufficient oxygenation via diffusion to prevent ischemia in response to arterial occlusion.

Methods and Results—

We studied
gridlock
mutant embryos that suffer a permanently occluded aorta and show that these restore aortic blood flow by collateral vessels. We phenocopied
gridlock
mutants by laser-induced proximal aortic occlusion in transgenic Fli1:eGFP/GATA1:dsRED embryos. Serial imaging showed these restore aortic blood flow via collateral vessels by recruitment of preexisting endothelium in a manner similar to
gridlocks
. Collateral aortic blood flow in
gridlock
mutants was dependent on both nitric oxide and myeloid cells. Confocal microscopy of transgenic
gridlock
/Fli1:eGFP mutants demonstrated no aberrant angiogenic response to the aortic occlusion. qPCR of HIF1α expression confirmed the absence of hypoxia in this model system.

Conclusions—

We conclude that NO and myeloid cell-dependent collateral vessel development is an evolutionarily ancient response to arterial occlusion and is able to proceed in the absence of ischemia.
Differential Effect of Hypolipidemic Drugs on Lipoprotein-Associated Phospholipase A
2
Authors: Saougos Vasilios G. , Tambaki Afroditi P. , Kalogirou Mihalis , Kostapanos Michael , Gazi Irene F. , Wolfert Robert L. , Elisaf Moses , Tselepis Alexandros D.
Published: July 2007

Objective—

Lipoprotein-associated phospholipase A
2
(Lp-PLA
2
) is a predictor for incident atherosclerotic disease. We investigated the effect of 3 hypolipidemic drugs that exert their action through different mechanisms on plasma and lipoprotein-associated Lp-PLA
2
activity and mass.

Methods and Results—

In 50 patients with Type IIA dyslipidemia were administered rosuvastatin (10 mg daily), whereas in 50 Type IIA dyslipidemic patients exhibiting intolerance to previous statin therapy were administered ezetimibe as monotherapy (10 mg daily). Fifty patients with Type IV dyslipidemia were given micronised fenofibrate (200 mg daily). Low- and high-density lipoprotein (LDL and HDL, respectively) subclass analysis was performed electrophoretically, whereas lipoprotein subfractions were isolated by ultracentrifugation. Ezetimibe reduced plasma Lp-PLA
2
activity and mass attributable to the reduction in plasma levels of all LDL subfractions. Rosuvastatin reduced enzyme activity and mass because of the decrease in plasma levels of all LDL subfractions and especially the Lp-PLA
2
on dense LDL subfraction (LDL-5). Fenofibrate preferentially reduced the Lp-PLA
2
activity and mass associated with the VLDL+IDL and LDL-5 subfractions. Among studied drugs only fenofibrate increased HDL-associated Lp-PLA
2
(HDL-Lp-PLA
2
) activity and mass attributable to a preferential increase in Lp-PLA
2
associated with the HDL-3c subfraction.

Conclusion—

Ezetimibe, rosuvastatin, and fenofibrate reduce Lp-PLA
2
activity and mass associated with the atherogenic apoB-lipoproteins. Furthermore, fenofibrate improves the enzyme specific activity on apoB-lipoproteins and induces the HDL-Lp-PLA
2
. The clinical implications of these effects remain to be established.
Association of Plasminogen Activator Inhibitor (PAI)-1 (SERPINE1) SNPs With Myocardial Infarction, Plasma PAI-1, and Metabolic Parameters
Authors: Morange P.E. , Saut N. , Alessi M.C. , Yudkin J.S. , Margaglione M. , Di Minno G. , Hamsten A. , Humphries S.E. , Tregouet D.A. , Juhan-Vague I.
Published: July 2007

Objective—

The purpose of this study was to investigate the effects of plasminogen activator inhibitor-1 (PAI-1) gene (SERPINE1) single nucleotide polymorphisms (SNPs) on the risk of myocardial infarction (MI), on PAI-1 levels, and factors related to the metabolic syndrome.

Methods and Results—

Eleven SNPs capturing the common genetic variation of the SERPINE1 gene were genotyped in the HIFMECH study. In the 510 male cases and their 543 age-matched controls, a significant gene-smoking interaction was observed. In nonsmokers, the rs7242-G allele was more frequent in cases than in controls (0.486 versus 0.382,
P
=0.013) whereas the haplotype derived from the rs2227631 (−844A>G)-G and rs2227683-A alleles was ≈3-fold lower in cases than in controls (0.042 versus 0.115,
P
=0.006). SERPINE1 haplotypes explained 3.5% (
P
=0.007) of the variability of PAI-1 levels, which was attributable to the combined effects of 3 SNPs, −844A>G, rs2227666, and rs2227694. The rs6092 (Ala15Thr) and rs7242 SNPs acted additively to explain 4.4% of the variability of plasma insulin levels and 1.6% of the variability of BMI (
P
<10
−3
and
P
=0.023, respectively).

Conclusions—

SERPINE1 haplotypes are mildly associated with plasma levels of PAI-1 and with the risk of MI in nonsmokers. They are also associated with insulin levels and BMI.
Carotid Intima-Media Thickness in Confirmed Prehypertensive Subjects
Authors: Femia Romana , Kozakova Michaela , Nannipieri Monica , Gonzales-Villalpando Clicerio , Stern Michael P. , Haffner Steven M. , Ferrannini Ele
Published: July 2007

Objective—

The purpose of this study was to test whether carotid intima-media thickness (IMT) is already increased in normotensive subjects who progress to hypertension (confirmed prehypertensives) independently of known determinants of vessel wall thickness.

Methods and Results—

Common carotid artery (CCA) far-wall IMT was measured (B-mode ultrasound) in 1536 subjects from the population-based Mexico City Diabetes Study at baseline and 3.5 years later. In the 136 confirmed prehypertensives, CCA-IMT (720 [253] μm, median[interquartile range]) was intermediate between normotensives (615 [140] μm) and hypertensives (725 [215] μm). After multiadjusting for gender, age, BMI, blood pressure, total cholesterol, antihypertensive therapy, and diabetes, converter status was independently associated with a higher CCA-IMT (+93±14 μm). At follow-up, CCA-IMT increased by 35 [180] μm. Gender, age, blood pressure, and presence of diabetes, but not the converter status, were significant independent predictors of CCA-IMT progression. In a model adjusting for gender, age, blood pressure (level, status and treatment), diabetes status, total and HDL-cholesterol, the G variant of the 45T/G polymorphism of the adiponectin gene was associated with a hazard ratio of 1.45 (95% CI: 1.04 to 2.01) of a baseline CCA-IMT in the top quintile.

Conclusions—

In confirmed prehypertensives, CCA-IMT is increased independently of blood pressure and known determinants of wall thickness, but short-term CCA-IMT progression is not accelerated.
Interferon-γ Induces Human Vascular Smooth Muscle Cell Proliferation and Intimal Expansion by Phosphatidylinositol 3-Kinase–Dependent Mammalian Target of Rapamycin Raptor Complex 1 Activation
Authors: Wang Yinong , Bai Yalai , Qin Lingfeng , Zhang Pei , Yi Tai , Teesdale Stephanie A. , Zhao Liping , Pober Jordan S. , Tellides George
Published: July 2007

Interferon (IFN)-γ, a cytokine characteristically expressed in arteriosclerotic diseases, acts directly on vascular smooth muscle cells to induce cellular proliferation and intimal expansion. Signaling by the mammalian target of rapamycin raptor complex, known as mTORC1, is associated with cell growth and is active within arteriosclerotic lesions but is not known to be triggered by proinflammatory factors in vascular smooth muscle cells. We investigated the mechanisms for the proarteriosclerotic effects of IFN-γ in the absence of leukocytes by exploiting the species specificity of this cytokine in a chimeric model of immunodeficient mouse recipients bearing human coronary artery grafts and intravenously inoculated with adenovirus encoding a human IFN-γ transgene. We found that IFN-γ–mediated vascular smooth muscle cell proliferation and intimal expansion were associated with phosphorylation of the mTORC1 effector ribosomal protein S6 kinase 1, that the graft morphological changes and S6 kinase 1 activation were inhibited by the mTORC1 inhibitor rapamycin in vivo, and that IFN-γ–induced mTORC1 signaling was dependent on phosphatidylinositol 3-kinase activity under serum-free conditions in vitro. Our work establishes an immunologic stimulus for mTORC1 signaling in vascular smooth muscle cells, emphasizes that mTORC1 activation is critical in immune-mediated vascular remodeling, and provides further mechanistic insight into the successful clinical application of rapamycin therapy for atherosclerosis and graft arteriosclerosis.
Modest Reductions of Cardiac Calsequestrin Increase Sarcoplasmic Reticulum Ca
2+
Leak Independent of Luminal Ca
2+
and Trigger Ventricular Arrhythmias in Mice
Authors: Chopra Nagesh , Kannankeril Prince J. , Yang Tao , Hlaing Thinn , Holinstat Izabela , Ettensohn Kristen , Pfeifer Karl , Akin Brandy , Jones Larry R. , Franzini-Armstrong Clara , Knollmann Björn C.
Published: July 2007

Cardiac calsequestrin–null mice (
Casq2
−/−
) display catecholaminergic ventricular tachycardia akin to humans with
CASQ2
mutations. However, the specific contribution of Casq2 deficiency to the arrhythmia phenotype is difficult to assess because
Casq2
−/−
mice also show significant reductions in the sarcoplasmic reticulum (SR) proteins junctin and triadin-1 and increased SR volume. Furthermore, it remains unknown whether Casq2 regulates SR Ca
2+
release directly or indirectly by buffering SR luminal Ca
2+
. To address both questions, we examined heterozygous (
Casq2
+/−
) mice, which have a 25% reduction in Casq2 but no significant decrease in other SR proteins.
Casq2
+/−
mice (n=35) challenged with isoproterenol displayed 3-fold higher rates of ventricular ectopy than
Casq2
+/+
mice (n=31;
P
<0.05). Programmed stimulation induced significantly more ventricular tachycardia in
Casq2
+/−
mice than in
Casq2
+/+
mice. Field-stimulated Ca
2+
transients, cell shortening, L-type Ca
2+
current, and SR volume were not significantly different in
Casq2
+/−
and
Casq2
+/+
myocytes. However, in the presence of isoproterenol, SR Ca
2+
leak was significantly increased in
Casq2
+/−
myocytes (
Casq2
+/−
0.18±0.02
F
ratio
versus
Casq2
+/+
0.11±0.01
F
ratio
, n=57, 60;
P
<0.01), resulting in a significantly higher rate of spontaneous SR Ca
2+
releases and triggered beats. SR luminal Ca
2+
measured using Mag-Fura-2 was not altered by Casq2 reduction. As a result, the relationship between SR Ca
2+
leak and SR luminal Ca
2+
was significantly different between
Casq2
+/−
and
Casq2
+/+
myocytes (
P
<0.01). Thus, even modest reductions in Casq2 increase SR Ca
2+
leak and cause ventricular tachycardia susceptibility under stress. The underlying mechanism is likely the direct regulation of SR Ca
2+
release channels by Casq2 rather than altered luminal Ca
2+
.
Habitual Physical Activity and Vascular Aging in a Young to Middle-Age Population at Low Cardiovascular Risk
Authors: Kozakova Michaela , Palombo Carlo , Mhamdi Leila , Konrad Thomas , Nilsson Peter , Staehr Peter Bisgaard , Paterni Marco , Balkau Beverley
Published: July 2007

Background and Purpose—

Regular endurance exercise has been shown to reduce the age-related increase in arterial stiffness that is thought to contribute to cardiovascular risk. The aim of this study was to evaluate the influence of age and habitual physical activity on carotid artery wall thickness and stiffness in a population of young to middle-age subjects at low cardiovascular risk.

Methods—

The study population consisted of 432 healthy subjects (166 men; mean±SD age, 43±8 years; range, 30 to 60 years) free of carotid atherosclerosis and with low coronary heart disease risk, as determined by the Framingham prediction score sheet. All subjects underwent B-mode ultrasonography of the extracranial carotid arteries and physical activity assessment by actigraph, an accelerometer capable of monitoring the intensity and duration of body movements. The intima-media thickness of the common carotid artery was measured on ultrasound images, along with systodiastolic changes in luminal diameter, and indices of carotid stiffness were calculated.

Results—

Intima-media thickness and carotid stiffness increased with age in both men and women (
r
=0.24 to 0.52,
P
<0.001). The magnitude of objectively assessed daily physical activity was negatively related to indices of carotid stiffness (
r
from −0.20 to −0.25,
P
<0.001) but not to intima-media thickness. In multivariate regression analyses that included several cardiovascular risk factors such as obesity, blood pressure, plasma lipids, and smoking habits, age and physical activity were independently related to carotid stiffness.

Conclusions—

This study provides cross-sectional evidence that habitual physical activity is inversely related to the age-dependent increase in carotid wall stiffness in a young to middle-age population at low risk.
Antiplatelets Versus Anticoagulation in Cervical Artery Dissection
Authors: Engelter Stefan T. , Brandt Tobias , Debette Stéphanie , Caso Valeria , Lichy Christoph , Pezzini Alessandro , Abboud Sherine , Bersano Anna , Dittrich Ralf , Grond-Ginsbach Caspar , Hausser Ingrid , Kloss Manja , Grau Armin J. , Tatlisumak Turgut , Leys Didier , Lyrer Philippe A.
Published: July 2007

Background and Purpose—

The widespread preference of anticoagulants over antiplatelets in patients with cervical artery dissection (CAD) is empirical rather than evidence-based.

Summary of Review—

This article summarizes pathophysiological considerations, clinical experiences, and the findings of a systematic metaanalysis about antithrombotic agents in CAD patients. As a result, there are several putative arguments in favor as well as against immediate anticoagulation in CAD patients.

Conclusions—

A randomized controlled trial comparing antiplatelets with anticoagulation is needed and ethically justified. However, attributable to the large sample size which is required to gather meaningful results, such a trial represents a huge venture. This comprehensive overview may be helpful for the design and the promotion of such a trial. In addition, it could be used to encourage both participation of centers and randomization of CAD patients. Alternatively, antithrombotic treatment decisions can be customized based on clinical and paraclinical characteristics of individual CAD patients. Stroke severity with National Institutes of Health Stroke Scale score ≥15, accompanying intracranial dissection, local compression syndromes without ischemic events, or concomitant diseases with increased bleeding risk are features in which antiplatelets seem preferable. In turn, in CAD patients with (pseudo)occlusion of the dissected artery, high intensity transient signals in transcranial ultrasound studies despite (dual) antiplatelets, multiple ischemic events in the same circulation, or with free-floating thrombus immediate anticoagulation is favored.
Improvement in Bonding of Functional Elements with the Fiber Reinforced Polymer Structure by Means of Tailoring Technology
Authors: Molnár P. , Mitschang P. , Felhös D.
Published: July 2007

The development of sub-preforms is very often a vital step within the resin transfer molding composite technology, to manufacture 3D net shape preforms. This step can be especially necessary for the adaptation of metallic inserts in the ready to impregnate fibrous structure. Inserts can be brought into the structure by means of a stitch-based joining technology. Within this study, the bonding efficiency of metallic inserts in glass fiber reinforced composite with an epoxy matrix has been evaluated. The influence of different polyester sewing threads, stitch types, and sewing parameters on the mechanical properties of the stitched inserts were also investigated. The injected specimens were loaded with static tensile stress. During the destruction tests the maximum load force of a sewn insert and the failure mode has been observed. The first section of the inserts failure mechanism was finite element analysis modeled up to the first delamination phase. The finite element analysis confirmed the results of the experimental studies.
Why Do Countries Commit to Human Rights Treaties?
Authors: Hathaway Oona A.
Published: July 2007

This article examines states' decisions to commit to human rights treaties. It argues that the effect of a treaty on a state—and hence the state's willingness to commit to it—is largely determined by the domestic enforcement of the treaty and the treaty's collateral consequences. These broad claims give rise to several specific predictions. For example, states with less democratic institutions will be no less likely to commit to human rights treaties if they have poor human rights records, because there is little prospect that the treaties will be enforced. Conversely, states with more democratic institutions will be less likely to commit to human rights treaties if they have poor human rights records—precisely because treaties are likely to lead to changes in behavior. These predictions are tested by examining the practices of more than 160 countries over several decades.
Study of the Influence of Immersion on the Carbon Fiber/Epxoy Composites
Authors: Lv Xiaojun , Zhang Qi , Li Xiaofei , Xie Guojun
Published: July 2007

Carbon fiber/epoxy composites are studied in this paper. In order to decide the important factors to the performance of the composite materials, many corrosion tests were carried out by means of immersion. The test conditions were decided by the Normal (orthogonal test) Table of three factors, i.e., temperature, concentration and the test period. The results showed that the immersion caused the properties of composites to deteriorate and that the solution temperature was the most important factor among the three factors.
Multifactorial Regulation of Daily Rhythms in Expression of the Metabolically Responsive Gene Spot14 in the Mouse Liver
Authors: Ishihara Akinori , Matsumoto Eriko , Horikawa Kazumasa , Kudo Takashi , Sakao Eiko , Nemoto Ayako , Iwase Katsuro , Sugiyama Hajime , Tamura Yutaka , Shibata Shigenobu , Takiguchi Masaki
Published: July 2007

Spot14 is a putative transcriptional regulator for genes involved in fatty acid synthesis. The Spot14 gene is activated in response to lipogenic stimuli such as dietary carbohydrate and is also under circadian regulation. The authors investigated factors responsible for daily oscillation of Spot14 expression. If mice were kept under a 12-h light/12-h dark cycle with ad libitum feeding, Spot14 mRNA levels in the liver reached a peak at an early dark period when mice, as nocturnal animals, start feeding. Under fasting, while Spot14 mRNA levels were generally decreased, the rhythmicity was still maintained, suggesting contribution of both nutritional elements and circadian clock factors on robust rhythmicity of Spot14 expression. Effects of circadian clock factors were confirmed by the observations that the circadian rhythm of Spot14 expression was seen also under the constant darkness and that the rhythmicity was lost in Clock mutant mice. When mice were housed in short-photoperiod (6-h light/18-h dark) and long-photoperiod (18-h light/6-h dark) cycles, rhythms of Spot14 mRNA levels were phase advanced and phase delayed, respectively, being concordant with the notion that Spot14 expression is under the control of the light-entrainable oscillator. As for nutritional mediators, in the liver of db/ db mice exhibiting hyperinsulinemia-accompanied hyperglycemia, Spot14 mRNA levels were constantly high without apparent rhythmicity, consistent with previous observations for strong activation of the Spot14 gene by glucose and insulin. Restricted feeding during the 4-h mid-light period caused a phase advance of the Spot14 expression rhythm. On the other hand, restricted feeding during the 4-h mid-dark period led to damping of the rhythmicity, apparently resulting from the separation of phases between effects of the light/dark cycle and feeding on Spot14 expression. Thus, the daily rhythm of Spot14 expression in the liver is under the control of the light-entrainable oscillator, food-entrainable oscillator, and food-derived nutrients, in a separate or cooperative manner.
Tumor Suppression and Circadian Function
Authors: Chen-Goodspeed Misty , Cheng Chi Lee
Published: July 2007

Circadian clock and cell division cycle are two fundamental biological processes. The circadian clock is the body's molecular time-keeping system, while the cell division cycle regulates development and cellular renewal. The expression of cell cycle genes such as Wee1, Cyclins, and c-Myc are under circadian control and could be directly under the regulation of the circadian transcriptional complex. This complex is composed of heterodimer transactivators CLOCK/NPAS2 with BMAL1, which regulate the transcription of PER1, PER2, CRY1, and CRY2. In turn, the repressors CRY1 and CRY2 turn off the gene expressions of Per1/Per2, Cry1/Cry2 in a periodic manner by acting on the transcriptional complex. Two of these circadian rhythm regulators, PER1 and PER2, have now been linked to DNA damage response pathways in a series of papers that examined gene dosage. Overexpression of either Per1 or Per2 in cancer cells inhibits their neoplastic growth and increases their apoptotic rate. In vivo studies showed that mice deficient in mPer2 showed significant higher incidences of tumor development after genotoxic stress. Loss and dysregulation of Per1 and Per2 gene expression have been found in many types of human cancers. Recent studies demonstrate that both PER1 and PER2 are involved in ATM-Chk1/Chk2 DNA damage response pathways and implicate normal circadian function as a factor in tumor suppression.
Going Around the Boss
Authors: Kassing Jeffrey W.
Published: July 2007

This study explores outcomes associated with circumvention (i.e., dissenting by going around or above one's supervisor). Employees completed a survey instrument in which they provided a dissent account detailing a time when they practiced circumvention. Several themes regarding relational and organizational outcomes emerged from an interpretive analysis of the data. Circumvention resulted predominantly in relational deterioration with one's supervisor, but in many cases it led to neutrality, compromise, relationship development, and understanding. Although organizational-level outcomes most often produce results that are favorable for dissenters, they also include triggering agent sanctions, organizational improvement, absence of corrective action, and disadvantageous outcomes for the dissenter.
Organizational Communication Comes Out
Authors: Cheney George
Published: July 2007

This essay celebrates the ways in which organizational communication scholars have engaged contemporary issues of social and economic justice but asks us to take the next step to bring our energies and insights together with our listening skills and compassion to the wider community.
The Role of Interphase on Micro- to Macroscopic Responses and Prediction for Initiation of Debonding Damage of Glass—Fiber Reinforced Polycarbonate
Authors: Esmaeili N. , Tomita Y.
Published: July 2007

A computational model based on large-deformation finite element method (FEM) analysis is developed and used to evaluate the interaction between the microstructure and the heterogeneous deformation behavior of ternary composites on micro- to macroscopic scales. To uncover the influence of the plastic interphase layer on the stress—strain behavior of the three-phase system under constant strain-rate loading, the analyses of two different types of polymers with different Poisson's ratios are performed. In particular, we investigate the effects of the interphase on the normal stress at the fiber surface to predict the initiation of glass fiber—polymer matrix debonding damage. An interphase with stiffness well below that of the matrix shows a suitable effect on the micro- to macroscopic deformation behavior and suppresses the initiation of debonding, while an interphase Poisson's ratio between that of the fiber and the matrix is preferable. Furthermore, computational simulation has been performed to clarify the effects of the interphase thickness and fiber volume fraction on the normal stress at the fiber surface. The results obtained using the models suggest the realization of favorable interphase properties for suppressing the initiation of debonding at the fiber surface and improving the functionality of the reinforced polymer.
Protection from CMV infection in immunodeficient hosts by adoptive transfer of memory B cells
Authors: Klenovsek Karin , Weisel Florian , Schneider Andrea , Appelt Uwe , Jonjic Stipan , Messerle Martin , Bradel-Tretheway Birgit , Winkler Thomas H. , Mach Michael
Published: July 2007

Severe disease associated with cytomegalovirus (CMV) infection is still a major problem in patients who undergo transplantation. Support of the patients' immune defense against the virus is a major goal in transplantation medicine. We have used the murine model of CMV (MCMV) to investigate the potential of a cell-based strategy to support the humoral antiviral immune response. Immunocompetent C57BL/6 mice were infected with MCMV, and memory B cells from the immune animals were adoptively transferred into T-cell– and B-cell–deficient RAG-1−/− mice. Following MCMV infection, a virus-specific IgG response developed within 4 to 7 days in the recipient animals. Concomitantly, a significant reduction in viral titers and DNA copies in several organs was observed. In addition, the memory B-cell transfer provided long-term protection from the lethal course of the infection that is invariably seen in immunodeficient animals. Transfer of memory B cells was also effective in protecting from an already ongoing viral infection, indicating a therapeutic potential of virus-specific memory B cells. T cells were not involved in this process. Our data provide evidence that a cell-based strategy to support the humoral immune response can be effective to combat infectious pathogens in severely immunodeficient hosts.
Crucial pathophysiological role of CXCR2 in experimental ulcerative colitis in mice
Authors: Buanne Pasquale , Di Carlo Emma , Caputi Lorenzo , Brandolini Laura , Mosca Marco , Cattani Franca , Pellegrini Luigi , Biordi Leda , Coletti Gino , Sorrentino Carlo , Fedele Guido , Colotta Francesco , Melillo Gabriella , Bertini Riccardo
Published: July 2007

Polymorphonuclear leukocyte infiltration and activation into colonic mucosa are believed to play a pivotal role in mediating tissue damage in human ulcerative colitis (UC). Ligands of human CXC chemokine receptor 1 and 2 (CXCR1/R2) are chemoattractants of PMN, and high levels were found in the mucosa of UC patients. To investigate the pathophysiological role played by CXCR2 in experimental UC, we induced chronic experimental colitis in WT and CXCR2−/− mice by two consecutive cycles of 4% dextran sulfate sodium administration in drinking water. In wild-type (WT) mice, the chronic relapsing of DSS-induced colitis was characterized by clinical signs and histopathological findings that closely resemble human disease. CXCR2−/− mice failed to show PMN infiltration into the mucosa and, consistently with a key role of PMN in mediating tissue damage in UC, showed limited signs of mucosal damage and reduced clinical symptoms. Our data demonstrate that CXCR2 plays a key pathophysiological role in experimental UC, suggesting that CXCR2 activation may represent a relevant pharmacological target for the design of novel pharmacological treatments in human UC.
β-Glucan ofCandida albicanscell wall causes the subversion of human monocyte differentiation into dendritic cells
Authors: Nisini Roberto , Torosantucci Antonella , Romagnoli Giulia , Chiani Paola , Donati Simona , Gagliardi Maria Cristina , Teloni Raffaela , Sargentini Valeria , Mariotti Sabrina , Iorio Egidio , Cassone Antonio
Published: July 2007

The functional consequences of treating human monocytes with purified and chemically characterized Candida albicans β-glucan—a major microbial pathogen associated molecular pattern—on their differentiation into dendritic cells (DC) were investigated. We show here that β-glucan-treated monocytes differentiated into mature DC (Glu-MoDC) with altered phenotype and functional behavior, similarly to DC derived from C. albicans germ-tubes-infected monocytes (Gt-MoDC). They failed to express CD1a and to up-regulate CD80 and DR molecules. Moreover, they produced IL-10 but not IL-12 and primed naive T cells without inducing their functional polarization into effector cells. Since C. albicans β-glucan is a mixture of both β-(1,3) and β-(1,6) glucan, we investigated their relative contribution by the use of non-Candida β-glucan structural analogs. We found that high molecular weight (MW) glucans β−(1,6) pustulan and β-(1,3) curdlan totally mimicked the effect of C. albicans β-glucan, while the low MW β-(1,3) glucan laminarin did not have any effect. Because β-glucan is a common constituent of all fungi and is abundantly released in vivo during systemic fungal infection, this novel effect of β-glucan has potential implications for host-parasite relationship in candidiasis and other mycoses. In particular, our data suggest that β-glucan could bias noninfected, bystander monocytes, thus aggravating the general immunodeficiency, predisposing to systemic fungal infection.