Flow-induced dilation of skeletal muscle feed arteries: relevance to exercise hyperemia

During exercise, an increase in blood flow to working skeletal muscle is accomplished by dilation of arteries and arterioles supplying the muscle. Arterioles, located within contracting muscle, are exposed to dilatory metabolites released by the muscle; however, the mechanism by which feed arteries, located external to the muscle, dilate is still unknown. One potential mechanism for feed artery dilation is flow-induced dilation, occurring when arteries dilate in response to increased vascular wall shear stress. Shear stress is the frictional force between blood and the arterial wall, which increases when blood flow velocity increases. Data from previous in vitro experiments (8) indicate that flow-induced dilation in rat soleus feed arteries occurs at blood flow levels that are far less than normal resting blood flow in conscious rats. This data led to the conclusion that flow-induced dilation was not a plausible mechanism to explain the increase in blood flow during exercise. Furthermore, the soleus muscle is primarily composed of slow-oxidative fibers and used in maintaining posture; thus, it receives a substantial amount of blood flow at rest. We sought to test whether flow-induced dilation could contribute to exercise hyperemia in rat extensor digitorum longus muscle, primarily composed of fast-glycolytic fibers, and rat gastrocnemius, a muscle of mixed fiber type (4). The differences in fiber type of each muscle may be a factor in how the feed arteries dilate during exercise. The purpose of this study was to determine if flow-induced dilation potentially contributes to exercise hyperemia in rat extensor digitorum longus and gastrocnemius muscle feed arteries, EDLFA and GFA, respectively. In this study, blood flow was induced through the arteries and corresponding flow measurements (µl/min) were collected. The flow values were used to calculate intraluminal wall shear stress in the arteries and then compared to calculated in vivo shear stress values from previously published studies (1,2,3,7,10,11,12,13,14,15). We hypothesized that flow-induced dilation in GFA and EDLFA occurs at shear stress values lower than the shear stress normally present in non-exercising rats. This would preclude flow-induced dilation from causing the dilation of feed arteries to gastrocnemius and EDL muscles in exercise

Steroid Hormone Synthesis by Vaccinia Virus Suppresses the Inflammatory Response to Infection

The 3β-hydroxysteroid dehydrogenase (3β-HSD) isoenzymes play a key role in cellular steroid hormone synthesis. Vaccinia virus (VV) also synthesizes steroid hormones with a 3β-HSD enzyme (v3β-HSD) encoded by gene A44L. Here we examined the effects of v3β-HSD in VV disease using wild-type (vA44L), deletion (vΔA44L), and revertant (vA44L-rev) viruses in a murine intranasal model. Loss of A44L was associated with an attenuated phenotype. Early (days 1–3) after infection with vΔA44L or control viruses the only difference observed between groups was the reduced corticosterone level in lungs and plasma of vΔA44L-infected animals. Other parameters examined (body weight, signs of illness, temperature, virus titres, the pulmonary inflammatory infiltrate, and interferon [IFN]-γ levels) were indistinguishable between groups. Subsequently, vΔA44L-infected animals had reduced weight loss and signs of illness, and displayed a vigorous pulmonary inflammatory response. This was characterized by rapid recruitment of CD4+ and CD8+ lymphocytes, enhanced IFN-γ production and augmented cytotoxic T lymphocyte activity. These data suggest that steroid production by v3β-HSD contributes to virus virulence by inhibiting an effective inflammatory response to infection

Blunt trauma induced splenic blushes are not created equal

<p>Abstract</p> <p>Background</p> <p>Currently, evidence of contrast extravasation on computed tomography (CT) scan is regarded as an indication for intervention in splenic injuries. In our experience, patients transferred from other institutions for angioembolization have often resolved the blush upon repeat imaging at our hospital. We <it>hypothesized </it>that not all splenic blushes require intervention.</p> <p>Methods</p> <p>During a 10-year period, we reviewed all patients transferred with blunt splenic injuries and contrast extravasation on initial postinjury CT scan.</p> <p>Results</p> <p>During the study period, 241 patients were referred for splenic injuries, of whom 16 had a contrast blush on initial CT imaging (88% men, mean age 35 ± 5, mean ISS 26 ± 3). Eight (50%) patients were managed without angioembolization or operation. Comparing patients with and without intervention, there was a significant difference in admission heart rate (106 ± 9 <it>vs </it>83 ± 6) and decline in hematocrit following transfer (5.3 ± 2.0 <it>vs </it>1.0 ± 0.3), but not in injury grade (3.9 ± 0.2 <it>vs </it>3.5 ± 0.3), systolic blood pressure (125 ± 10 <it>vs </it>115 ± 6), or age (38.5 ± 8.2 <it>vs </it>30.9 ± 4.7). Of the 8 observed patients, 3 underwent repeat imaging immediately upon arrival with resolution of the blush. In the intervention group, 4 patients had ongoing extravasation on repeat imaging, 2 patients underwent empiric embolization, and 2 patients underwent splenectomy for physiologic indications.</p> <p>Conclusions</p> <p>For blunt splenic trauma, evidence of contrast extravasation on initial CT imaging is not an absolute indication for intervention. A period of observation with repeat imaging could avoid costly, invasive interventions and their associated sequelae.</p

Effect of active immunization against growth hormone releasing factor on concentrations of somatotropin and insulin-like growth factor I in lactating beef cows

Two experiments were conducted to determine the effects of immunoneutralization of growth hormone-releasing factor [GRF(1–29)-NH2] on concentrations of somatotropin (ST) and insulin-like growth factor I (IGF-I) in lactating beef cows. In Experiment 1, multiparous Hereford cows were immunized against 2 mg GRF(1–29)-(Gly)4-Cys-NH2 conjugated to human serum albumin (GRFi, n=3) or 2 mg human serum albumin (HSAi, n=3) at 52 ± 1 d prior to parturition. Boosters (1 mg) were administered on days 12, 40 and 114 postpartum (pp). Serum samples were collected at 15-min intervals for 5 hr on days 18, 46 and 120 pp, followed by administration (IV) of an opioid agonist (FK33-824; 10 μg/kg) and an antagonist (naloxone; .5 mg/kg) at hours 5 and 7, respectively. A GRF-analog ([desamino-Tyr1, D-Ala2, Ala15] GRF (1–29)-NH2; 3.5 μg/kg) and arginine (.5 g/kg) were administered at hour 10 on days 47 and 121, respectively. Percentage binding of [125I]GRF (1:100 dilution of serum) 28 d after primary immunization was greater in GRFi (14.3 ± 4.9) than in HSAi (.7 ± .3) cows. Binding increased to 29.3 ± 6.5% after first booster in GRFi cows. Episodic release of ST was abolished by immunization against GRF; concentration and frequency of release of ST were lower (P125I]GRF, absence of pulsatile release of ST, low concentrations of ST and IGF-I and failure of ST to increase after IV opioid agonist or arginine

Are upright lateral cervical radiographs in the obtunded trauma patient useful? A retrospective study

BACKGROUND: The best method for radiographic "clearance" of the cervical spine in obtunded patients prior to removal of cervical immobilization devices remains debated. Dynamic radiographs or MRI are thought to demonstrate unstable injuries, but can be expensive and cumbersome to obtain. An upright lateral cervical radiograph (ULCR) was performed in selected patients to investigate whether this study could provide this same information, to enable removal of cervical immobilization devices in the multiple trauma patient. METHODS: We retrospectively reviewed our experience with ULCR in 683 blunt trauma victims who presented over a 3-year period, with either a Glasgow Coma Score <13 or who were intubated at the time of presentation. RESULTS: ULCR was performed in 163 patients. Seven patients had studies interpreted to be abnormal, of which six were also abnormal, by either CT or MRI. The seventh patient's only abnormality was soft tissue swelling; MRI was otherwise normal. Six patients had ULCR interpreted as normal, but had abnormalities on either CT or MRI. None of the missed injuries required surgical stabilization, although one had a vertebral artery injury demonstrated on subsequent angiography. ULCR had an apparent sensitivity of 45.5% and specificity of 71.4%. CONCLUSION: ULCR are inferior to both CT and MRI in the detection of cervical injury in patients with normal plain radiographs. We therefore cannot recommend the use of ULCR in the obtunded trauma patient

I-Brane Inflow and Anomalous Couplings on D-Branes

We show that the anomalous couplings of $D$-brane gauge and gravitational fields to Ramond-Ramond tensor potentials can be deduced by a simple anomaly inflow argument applied to intersecting $D$-branes and use this to determine the eight-form gravitational coupling.Comment: 8 pages, harvmac, no figure

An Automated Image-Based Method for Rapid Analysis of Chlamydia Infection as a Tool for Screening Antichlamydial Agents

This is the published version. Copyright American Society for MicrobiologyA major limitation in the identification of novel antichlamydial compounds is the paucity of effective methods for large-scale compound screening. The immunofluorescence assay is the preferred approach for accurate quantification of the intracellular growth of Chlamydia. In this study, an immunofluorescence image-based method (termed image-based automated chlamydial identification and enumeration [iBAChIE]) was customized for fully automated quantification of Chlamydia infection using the freely available open-source image analysis software program CellProfiler and the complementary data exploration software program CellProfiler Analyst. The method yielded enumeration of different species and strains of Chlamydia highly comparably to the conventional manual methods while drastically reducing the analysis time. The inhibitory capability of established antichlamydial activity was also evaluated. Overall, these data support that iBAChIE is a highly effective tool for automated quantification of Chlamydia infection and assessment of antichlamydial activities of molecules. Furthermore, iBAChIE is expected to be amenable to high-throughput screening studies for inhibitory compounds and fluorescently labeled molecules to study host-pathogen interactions

Independent evaluation of a simple clinical prediction rule to identify right ventricular dysfunction in patients with shortness of breath

BACKGROUND: Many patients have unexplained persistent dyspnea after negative computed tomographic pulmonary angiography (CTPA). We hypothesized that many of these patients have isolated right ventricular (RV) dysfunction from treatable causes. We previously derived a clinical decision rule (CDR) for predicting RV dysfunction consisting of persistent dyspnea and normal CTPA, finding that 53% of CDR-positive patients had isolated RV dysfunction. Our goal is to validate this previously derived CDR by measuring the prevalence of RV dysfunction and outcomes in dyspneic emergency department patients. METHODS: A secondary analysis of a prospective observational multicenter study that enrolled patients presenting with suspected PE was performed. We included patients with persistent dyspnea, a nonsignificant CTPA, and formal echo performed. Right ventricular dysfunction was defined as RV hypokinesis and/or dilation with or without moderate to severe tricuspid regurgitation. RESULTS: A total of 7940 patients were enrolled. Two thousand six hundred sixteen patients were analyzed after excluding patients without persistent dyspnea and those with a significant finding on CTPA. One hundred ninety eight patients had echocardiography performed as standard care. Of those, 19% (95% confidence interval [CI], 14%-25%) and 33% (95% CI, 25%-42%) exhibited RV dysfunction and isolated RV dysfunction, respectively. Patients with isolated RV dysfunction or overload were more likely than those without RV dysfunction to have a return visit to the emergency department within 45 days for the same complaint (39% vs 18%; 95% CI of the difference, 4%-38%). CONCLUSION: This simple clinical prediction rule predicted a 33% prevalence of isolated RV dysfunction or overload. Patients with isolated RV dysfunction had higher recidivism rates and a trend toward worse outcomes

KLF9 and JNK3 Interact to Suppress Axon Regeneration in the Adult CNS

Neurons in the adult mammalian CNS decrease in intrinsic axon growth capacity during development in concert with changes in Krüppel-like transcription factors (KLFs). KLFs regulate axon growth in CNS neurons including retinal ganglion cells (RGCs). Here, we found that knock-down of KLF9, an axon growth suppressor that is normally upregulated 250-fold in RGC development, promotes long-distance optic nerve regeneration in adult rats of both sexes. We identified a novel binding partner, MAPK10/JNK3 kinase, and found that JNK3 (c-Jun N-terminal kinase 3) is critical for KLF9\u27s axon-growth-suppressive activity. Interfering with a JNK3-binding domain or mutating two newly discovered serine phosphorylation acceptor sites, Ser106 and Ser110, effectively abolished KLF9\u27s neurite growth suppression in vitro and promoted axon regeneration in vivo. These findings demonstrate a novel, physiologic role for the interaction of KLF9 and JNK3 in regenerative failure in the optic nerve and suggest new therapeutic strategies to promote axon regeneration in the adult CNS

Developmental Morphology Of Tropical Sorghum And Sorghum X Sudangrass

Tropical sorghum and sorghum x sudangrass are known to be efficient scavengers of soil nitrogen and are important forage crops in the U.S. Nitrate contamination of groundwater due to disposal of organic wastes and excessive fertilization is a major concern in the Central Great Plains. A common disposal method of municipal wastes is application to fallow cropland. Quantification of the developmental morphology of tropical sorghum and sorghum x sudangrass is important to developing management strategies that allow multiple applications of organic wastes to optimize nitrogen removal and dry matter production. The objective of this study was to quantify the developmental morphology of tropical sorghum and sorghum x sudangrass irrigated at levels approximating transpiration and evaporative demand. Tropical sorghum mean stage by count (MSC) was 33% lower than MSC for sorghum x sudangrass in September. Leaf-to-stem ratio was greater for tropical sorghum than sorghum x sudangrass throughout most of the growing season. Dry matter per plant was as much as 30% greater for sorghum x sudangrass, although values were nearly equal at the end of the growing season