Isometric responses of rat extensor digitorum longus and soleus neuromuscular systems to abnormal extracellular calcium and magnesium concentrations

A hypothesis that altering extracellular concentrations of calcium and magnesium (Ca(\u27++)e, Mg(\u27++)e) would produce quantitatively different effects on the neurally evoked isometric responses of slow muscles, as represented by soleus (SOL), and fast muscles, as represented by extensor digitorum longus (EDL) of the rat, was tested;Isometric twitch and tetanic tensions, in response to nerve and muscle stimulation, were recorded in situ from animals with intact vascular systems and animals which had one hind limb perfused with a normal Krebs solution or an altered Krebs solution. Four combinations of altered Ca(\u27++)e and Mg(\u27++)e were perfused to determine whether transmission would be affected more at one type of neuromuscular junction than at the other;In response to decreased Ca(\u27++)e alone and decreased Ca(\u27++)e and increased Mg(\u27++)e, single twitch tension decreased less in the EDL than in the SOL neuromuscular system; tetanic tension decreased more in the EDL than in the SOL

DPOAEs in Children With Sickle Cell Disease

The purpose of this study was to investigate distortion product otoacoustic emissions (DPOAEs) in young normal-hearing children with sickle cell disease (SCD). It was hypothesized that the prevalence of DPOAEs and response amplitudes would be lower than those in children with normal hemoglobin due to suspected compromised cochlear function as a result of vaso-occlusive events characteristic of SCD. Twenty African-American children with SCD and 15 African-American children with normal hemoglobin participated. Distortion product OAEs were evoked by thirteen primary tone pairs with f2 frequencies ranging from 1000 to 4500 Hz. The primary tones were presented at and L1 and L2 levels of 70 and 60 dB SPL (high) and 50 and 40 dB SPL (low), respectively. The findings of this study were completely unexpected and contrary to our original hypotheses. The likelihood of detecting a DPOAE response was not related to the clinical status of the children. Distortion product OAE amplitudes were significantly larger for children with SCD (p = .01). Educational Objectives: After completing this article the reader will (1) have a basic knowledge of the audiometric complications of sickle cell disease and (2) appreciate the differences in DPOAEs between young normal-hearing children with sickle cell DPOAEs in Children With Sickle Cell Disease 3 disease and young normal-hearing children with normal hemoglobin

Insights Into Elevated Distortion Product Otoacoustic Emissions In Sickle Cell Disease: Comparisons of Hydroxyurea-treated and Non-treated Young Children

Distortion product otoacoustic emissions (DPOAEs) were examined in 15 normal- hearing African-American children between the ages of 6 and 14 years with homozygous sickle cell disease (SCD), who were on a regimen of hydroxyurea (HDU), a drug that reduces inflammatory processes and symptoms of SCD; a matched group of 15 African- American children with homozygous SCD not on HDU; and 15 African-American children with normal hemoglobin. DPOAEs were evoked by 13 primary tone pairs with f2 frequencies ranging from 1000 to 4500 Hz. Increased DPOAE amplitudes, believed to be a precursor of eventual hearing loss, were evident in children with SCD who were not receiving HDU. Those taking HDU had DPOAE amplitudes similar to normal controls. These findings suggest that HDU, in addition to reducing symptoms of SCD, may play a role in inhibiting or preventing cochlear pathology and hearing loss in individuals with SCD. Key Words: distortion product otoacoustic emissions; sickle cell disease; hydroxyurea Abbreviations: ABR = auditory brainstem response; DPOAE = distortion product otoacoustic emission; HDU = hydroxyurea; HbSS = homozygous sickle cell disease; ICAM = intercellular adhesion molecule; M = mean; OAE = otoacoustic emission; p = probability; PECAM = platelet-endothelial cell adhesion molecule SCD = sickle cell disease; SD = standard deviation of the mean; SOAE = spontaneous otoacoustic emission; TEOAE = transient evoked otoacoustic emission; VCAM = vascular cell adhesion molecule

Use of pressure sensitive radiotelemetering capsule to study the canine gastric interdigestive complex

http://www.worldcat.org/oclc/8090557</p

The Role Of D-Dopachrome Tautomerase In Ischemia-Reperfusion In The Heart

THE ROLE OF D-DOPACHROME TAUTOMERASE IN ISCHEMIA-REPERFUSION IN THE HEART. Kwame Atsina, Dake Qi, Richard Bucala, Lawrence Young, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT. AMP-activated protein kinase (AMPK) is a well-known energy sensor that regulates cardiac metabolism. In the heart, it is also regulated by the pleiotropic cytokine, macrophage migration inhibitory factor (MIF) to protect the myocardium from ischemia-reperfusion injury. D-dopachrome tautomerase (DDT) is a novel protein that binds with high affinity to the MIF receptor, CD74, through which MIF regulates AMPK-mediated cardioprotection. However, the role of DDT in regulating the cardiac response to ischemia reperfusion is unknown. We investigated the role of DDT in regulating AMPK activation and cardiac injury during experimental ischemia/reperfusion in mouse hearts, rat papillary muscle and rat cardiomyocytes. To investigate the effect of CD74 and MIF deficiency on the heart during ischemia reperfusion, hearts were subjected to ischemia for 15 minutes (Langendorff perfusion) or mice were subjected to 20 minutes of coronary ligation. CD74-/- hearts exposed to ischemia-reperfusion injury had greater myocardial necrosis and contractile dysfunction, and decreased AMPK activation than Mif-/- hearts. To determine DDT expression in cardiac tissue, mouse hearts received baseline perfusion or were exposed to ischemia (perfused heart model) for 15 minutes. Hearts were fixed and immunohistochemistry staining with anti-MIF and anti-DDT antibody revealed that MIF and DDT are released from the heart in response to ischemia. To investigate the effect of antibody neutralization of MIF and DDT on AMPK activation and cardiac injury following ischemia-reperfusion, (1) rat papillary muscle and rat cardiomyocytes were subjected to 15 and 30 minutes of hypoxia respectively, and (2) mouse hearts were subjected to 15 minutes of ischemia via Langendorff perfusion mode. 100 ìg/mL of non-specific IgG, anti-DDT or anti-MIF antibody was administered to the medium or buffer prior to hypoxia or ischemia. Antibody neutralization of DDT and MIF impaired AMPK activation in all three animal models, and exacerbated myocardial necrosis and LV contractile functional recovery in the mouse hearts following ischemia. These findings demonstrate that DDT plays an important role in regulating AMPK activity and protecting the heart from ischemia-reperfusion

Isometric responses of rat extensor digitorum longus and soleus neuromuscular systems to abnormal extracellular calcium and magnesium concentrations

A hypothesis that altering extracellular concentrations of calcium and magnesium (Ca('++)e, Mg('++)e) would produce quantitatively different effects on the neurally evoked isometric responses of slow muscles, as represented by soleus (SOL), and fast muscles, as represented by extensor digitorum longus (EDL) of the rat, was tested;Isometric twitch and tetanic tensions, in response to nerve and muscle stimulation, were recorded in situ from animals with intact vascular systems and animals which had one hind limb perfused with a normal Krebs solution or an altered Krebs solution. Four combinations of altered Ca('++)e and Mg('++)e were perfused to determine whether transmission would be affected more at one type of neuromuscular junction than at the other;In response to decreased Ca('++)e alone and decreased Ca('++)e and increased Mg('++)e, single twitch tension decreased less in the EDL than in the SOL neuromuscular system; tetanic tension decreased more in the EDL than in the SOL.</p

Nanoparticles For Delivery Of Rapamycin To Glioblastoma And Glioblastoma-Derived Stem Cells

NANOPARTICLES FOR DELIVERY OF RAPAMYCIN TO GLIOBLASTOMA AND GLIOBLASTOMA-DERIVED STEM CELLS. Kofi-Buaku Atsina1, Jiangbing Zhou1,2, Toral Patel2, Joseph Piepmeier2, and W. Mark Saltzman 1; 1 Yale University, Department of Biomedical Engineering, New Haven, CT; 2 Yale University School of Medicine, Department of Neurosurgery, New Haven, CT· Treatment of glioblastoma remains a challenge primarily because of the difficulty of achieving effective drug delivery, and the relative resistance of cancer stem cells to conventional chemoradiotherapy· Delivery of small molecule drugs, like rapamycin that have shown some efficacy against glioblastoma in in vitro and in vivo studies, is often thwarted by short drug half-lives, systemic toxicity, first-pass metabolism, and the impenetrable blood brain barrier (BBB)· Polymeric nanoparticles have the potential to solve the afore-mentioned challenges by enabling better delivery to cells, stabilizing their contents, and achieving sustained release in a localized fashion · Particularly, ultrasmall nanoparticles improve upon the abilities of this technology by achieving better tumor distribution and cellular uptake· The purpose of this study was to investigate the effects of rapamycin delivery by ultrasmall poly (D,L-lactic-co-glycolic acid)(PLGA) nanoparticles on differentiated glioblastoma (GB) and glioblastoma-derived stem cells (GSCs) in vitro· Ultrasmall polymeric nanoparticles encapsulating rapamycin were fabricated and their effects on GB cells (U87) and GSCs (PS30, PS16, GS5) were examined and compared with free rapamycin· Viability of cells was approximated by measuring their metabolic activity using Thiazolyl Blue Tetrazolium Bromide (MTT) assay. Results demonstrate that rapamycin nanoparticles improve efficacy of delivery relative to free rapamycin as demonstrated by greater inhibition of growth in GB cells, but may also have some efficacy against GSCs

Conversion of Intermediate LIRADS Categories to Hepatocellular Carcinoma in patients with Chronic Hepatitis B: Korean Immigrant Experience

Introduction and Objective The Liver Imaging Reporting and Data System (LIRADS) was created to standardize the reporting and data collection of MR imaging for hepatocellular carcinoma (HCC) in high risk patients. The major categories for LIRADS have the following descriptors: LI-RADS 1 = Definitely benign LI-RADS 2 = Probably benign LI-RADS 3 = Intermediate probability for HCC LI-RADS 4 = Probably HCC LI-RADS 5 = Definitely HCC LI-RADS 5V = Definitely HCC with tumor in vein LI-RADS M = Probable malignancy, not specific for HCC LI-RADS T = Treated Observation However, there is a paucity of quantitative evidence for the progression of LIRADS 2, 3 and 4, (hereafter defined as intermediate LIRADS categories) to LIRADS 5. Our objective was to investigate the conversion of intermediate LIRADS categories to definite hepatocellular carcinoma (LIRADS 5) to help inform management decisions regarding treatment and better stratify imaging follow up for high-risk patients with intermediate LIRADS categories. Poster presented at: SCBT-MR in Salt Lake City, Utah.https://jdc.jefferson.edu/radiologyposters/1002/thumbnail.jp

Heparanase regulates EMT and cancer stem cell properties in prostate tumors

Prostate cancer displays a certain phenotypic plasticity that allows for the transition of cells from the epithelial to the mesenchymal state. This process, known as epithelial-mesenchymal transition (EMT), is one of the factors that give the tumor cells greater invasive and migratory capacity with subsequent formation of metastases. In addition, many cancers, including prostate cancer, are derived from a cell population that shows the properties of stem cells. These cells, called cancer stem cells (CSCs) or tumor-initiating cells, not only initiate the tumor process and growth but are also able to mediate metastasis and drug resistance. However, the impact of EMT and CSCs in prostate cancer progression and patient survival is still far from fully understood. Heparanase (HPSE), the sole mammalian endoglycosidase capable of degrading heparan sulfate (HS), is also involved in prostate cancer progression. We had previously proved that HPSE regulates EMT in non-cancerous pathologies. Two prostate cancer cell lines (DU145 and PC3) were silenced and overexpressed for HPSE. Expression of EMT and stemness markers was evaluated. Results showed that the expression of several EMT markers are modified by HPSE expression in both the prostate cancer cell lines analyzed. In the same way, the stemness markers and features are also modulated by HPSE expression. Taken together, the present findings seem to prove a new mechanism of action of HPSE in sustaining prostate cancer growth and diffusion. As for other tumors, these results highlight the importance of HPSE as a potential pharmacological target in prostate cancer treatment