Humeral fracture in arm wrestling: bone morphology as a permanent risk factor. Indications for safety measures in arm wrestling.

BACKGROUND: Arm wrestling has been recognized as a popular and potentially dangerous competition. Reports on injuries related to arm wrestling are increasing. The most important of these injuries are humeral shaft fractures. The generally accepted theory states that the shoulder joint is actively internally rotated against the opponent while the elbow is fixed in flexion resulting in enormous violent torque forces across the humeral shaft. METHODS: The reported fracture morphology seems similar so we theorized that the basis of this fracture type is the bone structure. There is no experimental model of the arm wrestling fracture other than a virtual one. We assess morphology of the humeral bone by means of the bone cutting procedures and to verify the theory that the structure of humeral bone is a basis of the arm-wrestling fracture by means of newly developed model on human bones. RESULTS: Results of the study suggest that the humeral shaft fracture morphology during arm wrestling is based on the spiral structure of the bone combined with the direction of the revolving, rotational force during the match. CONCLUSION: The safety rules of the arm-wrestling match based on results of our experimental study and the literature metaanalysis are also formulate.

Induced quantum dots and wires: electron storage and delivery.

We show that quantum dots and quantum wires are formed underneath metal electrodes deposited on a planar semiconductor heterostructure containing a quantum well. The confinement is due to the self-focusing mechanism of an electron wave packet interacting with the charge induced on the metal surface. Induced quantum wires guide the transfer of electrons along metal paths and induced quantum dots store the electrons in specific locations of the nanostructure. Induced dots and wires can be useful for devices operating on the electron spin. An application for a spin readout device is proposed.

Results of a 90-day safety assurance study with rats fed grain from corn borer-protected corn.

The results of a 90-day rat feeding study with grain from MON 810 corn (YieldGard Cornborer -- YieldGard Cornborer is a registered trademark of Monsanto Technology, LLC) that is protected against feeding damage from corn and stalk boring lepidopteran insects are presented. Corn borer protection was accomplished through the introduction of cry1Ab coding sequences into the corn genome for in planta production of a bioactive form of Cry1Ab protein. Grain from MON 810 and its near-isogenic control was separately formulated into rodent diets at levels of 11% and 33% (w/w) by Purina Mills, Inc. (PMI). All diets were nutritionally balanced and conformed to PMI specifications for Certified LabDiet (PMI Certified LabDiet 5002 is a registered trademark of Purina Mills, Inc.) 5002. There were a total of 400 rats in the study divided into 10 groups of 20 rats/sex/group. The responses of rats fed diets containing MON 810 were compared to those of rats fed grain from conventional corn varieties. Overall health, body weight, food consumption, clinical pathology parameters (hematology, blood chemistry, urinalysis), organ weights, and gross and microscopic appearance of tissues were comparable between groups fed diets containing MON 810 and conventional corn varieties. This study complements extensive agronomic, compositional and farm animal feeding studies with MON 810 grain, confirming that it is as safe and nutritious as grain from existing commercial corn varieties.

Results of a 90-day safety assurance study with rats fed grain from corn rootworm-protected corn.

The results of a 90-day rat feeding study with YieldGard (YieldGard Rootworm Corn is a registered trademark of Monsanto Technology, LLC.) Rootworm corn (MON 863) grain that is protected against feeding damage caused by corn rootworm larvae are presented. Corn rootworm-protection was accomplished through the introduction of a cry3Bb1 coding sequence into the corn genome for in planta production of a modified Cry3Bb1 protein from Bacillus thuringiensis. Grain from MON 863 and its near isogenic control were separately formulated into rodent diets at levels of 11% and 33% (w/w) by Purina Mills, Inc. Additionally, six groups of rats were fed diets containing grain from different conventional (non-biotechnology-derived) reference varieties. The responses of rats fed diets containing MON 863 were compared to those of rats fed grain from conventional corn varieties. All diets were nutritionally balanced and conformed to Purina Mills, Inc. specifications for Certified LabDiet 5002. There were a total of 400 rats in the study divided into 10 groups of 20 rats/sex/group. Overall health, body weight gain, food consumption, clinical pathology parameters (hematology, blood chemistry, urinalysis), organ weights, gross and microscopic appearance of tissues were comparable between groups fed diets containing MON 863 and conventional corn varieties. This study complements extensive agronomic, compositional and farm animal feeding studies with MON 863 grain, confirming that it is as safe and nutritious as existing conventional corn varieties.

Results of a 13 week safety assurance study with rats fed grain from glyphosate tolerant corn.

The current study presents the results of a 13 week feeding study in rats with grain from Roundup Ready corn which is tolerant to the herbicide glyphosate. Herbicide tolerance was accomplished through the introduction of cp4 epsps coding sequences into the corn genome for in planta production of CP4 EPSPS enzymes. Unlike related corn EPSPS enzymes, CP4 EPSPS enzymes are not inhibited by the herbicide glyphosate. Purina TestDiets formulated Roundup Ready corn grain into rodent diets at levels of 11 and 33% (w/w). The responses of rats fed diets containing Roundup Ready corn grain were compared to that of rats fed diets containing non-transgenic grain (controls). All diets were nutritionally balanced and conformed to Purina Mills, Inc. specifications for Certified LabDiet 5002. There were 400 rats in the study divided into 10 groups of 20 rats/sex/group. Overall health, body weight, food consumption, clinical pathology parameters (hematology, blood chemistry, urinalysis), organ weights, gross and microscopic appearance of tissues were comparable between groups fed diets containing Roundup Ready and control corn grain. This study complements extensive agronomic, compositional and farm animal feeding studies with Roundup Ready corn grain, confirming it is as safe and nutritious as existing commercial corn hybrids.

Intercellular exchange of class II MHC complexes: ultrastructural localization and functional presentation of adsorbed I-A/peptide complexes.

Activated rat T cells, like human T cells, synthesize class II MHC glycoproteins (MHCII) and absorb MHCII from neighboring T cells. This study focused on interactions of myelin basic protein (MBP)-specific T cells that either synthesized MHCII or absorbed MHCII during activation to assess cellular structures associated with presentation of functional MHCII/peptide complexes. Synthesis of MHCII by CD4(+)TCR(+) T cells involved I-A(+) multivesicular MHC class II-like compartments (MIIC), release of MHCII(+) vesicles, and expression of MHCII on a dendritic arborization. T-cell-mediated adsorption of MHCII was a saturable process that required close cell proximity, actin polymerization, and a permissive temperature. Adsorbed MHCII existed on vesicles that were intimately associated with the responder cell membrane. T cells bearing adsorbed vesicular MHCII presented antigen and were specifically lysed by CD4(+) T cell responders, but when labeled with anti-MHCII antibody were not susceptible to complement-mediated lysis. In summary, this study reveals vesicular compartments associated with synthesis and intercellular exchange of functional MHCII/peptide complexes.

Role of transverse tubules (T-tubules) in muscle glucose transport.

The first data to demonstrate glucose transporter translocation in muscle used membranes enriched in sarcolemma because it was assumed that this was the equivalent of the cell membrane of adipocytes. We studied translocation in intact human muscle using immunogold labeling of the GLUT4 transporter but found very little labeling on the sarcolemma. In contrast, there was abundant gold-labeling associated with the T-tubules and we proposed that glucose transport occurred across this membrane system. In a subsequent study using an entirely different technique, we labeled cell surface glucose transporters of rat muscle with a cell impermeant photolabel and demonstrated that a majority of the glucose transporters were translocated to T-tubules, not to the sarcolemma, in response to insulin. In this report we show for the first time that in insulin-plus contraction stimulated muscle, GLUT4 glucose transporters are associated with an area that we call the SCT complex (Sarcolemmal, Caveoli, T-tubule complex). This SCT complex may play an important role in delivering metabolites to the muscle under conditions, such as muscle contraction, when there is a very high requirement for glucose transport. From our data, and supporting data from other labs, we propose that the T-tubule membrane system plays a very important role in delivering nutrients to the center of skeletal muscle cells. Substrates can be quickly carried to the center of the muscle fiber where there are proteins to transport glucose (and presumably other substrates) across the T-tubule membrane to the site where it can be immediately utilized or stored. This hypothesis deserves serious consideration and experimental testing.

Normal forces and myofibrillar disruption after repeated eccentric exercise.

To investigate the "rapid-adaptation" phenomenon, we examined force, neural, and morphological adaptations in 12 subjects who performed 100 eccentric contractions with the quadriceps muscle (bout 1) and repeated the same exercise after a 2-wk hiatus (bout 2). Two days after bout 1, quadriceps muscle strength and surface electromyographic (EMG) activity declined approximately 37 and 28%, respectively, in the control group (n = 6). At day 2 after bout 1, significant increases occurred in patellar tendon reflex amplitude (approximately 25%), muscle soreness (fivefold), and serum creatine kinase (220%), and 65 +/- 12% of the total number of pixels in the EMG indicated myofibrillar disruption. At day 7 after bout 1, all variables returned to normal. At day 2 after bout 2, no significant changes occurred in force, EMG, creatine kinase, or soreness, but reflex amplitude increased, and 23 +/- 4% of the total number of pixels in the EMG still indicated myofibrillar disruption. The results suggest that the rapid force recovery following eccentric exercise is mediated at least in part by neural factors and that this recovery may occur independently of cell disruption.

Selective modulation of inducible nitric oxide synthase isozyme in myocardial infarction.

BACKGROUND: Inducible nitric oxide synthase (iNOS) is activated in cardiac disorders. We investigated the contribution of increased iNOS activity to the development of left ventricular dysfunction after myocardial infarction by selective inhibition of the isozyme. METHODS AND RESULTS: Male New Zealand rabbits were subjected to myocardial infarction. Animals were treated with either saline, S-methylisothiourea sulfate (SMT) (a selective iNOS inhibitor), or N(omega)-nitro-L-arginine (L-NNA) (a nonselective NOS inhibitor). Inducible and constitutive NOS (cNOS) activity, plasma NO(x), cGMP, hemodynamics, and myocardial blood flow were measured before and 5, 24, and 72 hours after coronary occlusion. Infarction 72 hours after occlusion resulted in increased myocardial iNOS activity, increased cardiac NO(x) production, and elevated cGMP levels. cNOS remained unchanged. Infarction increased left ventricular end-diastolic pressure (LVEDP) and decreased maximum +dP/dt and -dP/dt. L-NNA inhibited iNOS and cNOS activities and plasma NO(x) levels. L-NNA further increased LVEDP and reduced myocardial blood flow. Administration of SMT 72 hours after infarction significantly inhibited iNOS and cardiac NO(x) production but had no effects on cNOS. SMT improved left ventricular maximum +dP/dt and -dP/dt and decreased LVEDP. Myocardial blood flow in the remote myocardium increased. CONCLUSIONS: These findings suggest that induction of iNOS activity 72 hours after infarction exerts negative inotropic effects and contributes to the development of myocardial dysfunction; selective modulation of increased iNOS activity by SMT improves cardiac performance, enhances myocardial blood flow, and may be beneficial in the treatment of acute myocardial infarction.

S-methylisothiourea inhibits inducible nitric oxide synthase and improves left ventricular performance after acute myocardial infarction.

The contribution of increased inducible nitric oxide synthase (iNOS) activity to the development of left ventricular dysfunction after acute myocardial infarction (MI) was investigated New Zealand rabbits (n = 24) were randomly treated with either saline, S-methylisothiourea sulfate (SMT; selective iNOS inhibitor) or N-omega-nitro-L-arginine (NOLA; non-isoform selective NOS inhibitor). Left ventricular hemodynamics and myocardial blood flow were measured before coronary occlusion and on postoperative day 3 (POD 3). MI resulted in left ventricular dysfunction and increased myocardial iNOS activity. SMT and NOLA significantly inhibited iNOS activity; SMT, but not NOLA, significantly improved left ventricular maximum +dP/dt and decreased LVEDP; myocardial blood flow in the remote myocardium significantly increased after SMT. Induction of myocardial iNOS after MI on POD 3 contributes to the development of left ventricular dysfunction; modulation of iNOS activity by SMT improves left ventricular performance and may be beneficial after acute MI.

Induction of apoptosis in myocardial infarction and its possible relationship to nitric oxide synthase in macrophages.

Activated macrophages produce nitric oxide through the inducible form of nitric oxide synthase (iNOS). Previously, a significant increase of iNOS activity in macrophages in infarcted rabbit heart tissue was observed. The present study is concerned with the induction of apoptosis in macrophages and cardiomyocytes in infarcted rabbit heart tissue. The left anterior descending artery of rabbits was ligated. The heart was excised five hours, one, two, three, ten and twenty days later, and DNA was extracted from infarcted and non-infarcted region and subjected to electrophoresis. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) was carried out, and iNOS activity was measured by conversion of L-[14C]-arginine to L-[14C]-citrulline. Positive staining by TUNEL was seen in some cardiomyocytes five hours after coronary ligation and on postoperative day (POD) 1; internucleosomal DNA fragmentation was not noted. On POD 2 and 3, many infiltrating cells, immunohistochemically identified as macrophages, were positively stained by TUNEL; DNA fragmentation was also present. Apoptosis was not found on POD 10 and 20. The peak activity of iNOS was noted on POD 3, which corresponded with the induction of apoptosis. It is tempting to speculate that a causal relationship exists between increased iNOS formation and induction of apoptosis in macrophages in infarcted rabbit heart tissue.

Involvement of inducible nitric oxide synthase in the inflammatory process of myocardial infarction.

Inducible nitric oxide synthase (iNOS), which catalyzes the reaction of L-arginine to L-citrulline and nitric oxide (NO), plays an important role in immune-mediated cardiac disorders. The present report summarizes and discusses findings on the induction of NOS in myocardial infarction of rabbits. iNOS was significantly increased in infarcted myocardium 48 h after coronary artery ligation. The effect persisted for 14 days and declined thereafter. Immunohistochemical localization revealed macrophages as a major source of iNOS expression; iNOS expression was also present in infarcted human myocardium. Increased iNOS activity appeared to be related to the induction of apoptosis in infiltrating macrophages and cardiomyocytes. Moreover, preferential inhibition of iNOS by S-methylisothiourea sulfate (SMT) resulted in significant improvement of left ventricular performance and increased regional myocardial blood flow. These findings suggest that selective inhibition of iNOS activity may provide a therapeutic strategy in cardiac disorders such as myocardial infarction.

Lipid hydroperoxide-induced apoptosis: lack of inhibition by Bcl-2 over-expression.

Increased membrane lipid peroxidation has recently been implicated as being associated with apoptosis. In the present study the addition of 15-hydroperoxyeicosatetraenoic acid (15-HPETE) or 13-hydroperoxydodecadienoic acid (13-HPODE) to A3.01 T cells is shown to induce marked chromatin condensation coincident with DNA fragmentation, indicative of apoptosis. 15-HPETE also evoked an immediate and sustained rise in cytoplasmic calcium which was required for the induction of apoptosis. A3.01 cells transfected with the bcl-2 proto-oncogene were 6- to 8-fold more resistant to apoptotic killing by tumor necrosis factor-alpha, but only 0.4-fold more resistant to 15-HPETE. Thus, Bcl-2 is not capable of protecting cells from undergoing apoptosis following the direct addition of lipid hydroperoxides.

Inhibition of endothelial nitric oxide synthase by cytochrome P-450 reductase inhibitors.

Nitric oxide synthase (NOS) shows similarities to cytochrome P-450 reductase. The two enzymes catalyze the oxidation of N-omega-hydroxy-L-arginine by NADPH and oxygen to nitric oxide (NO) and citrulline. Nitric oxide synthase activity is inhibited by L-arginine analogs like N-omega-nitro-L-arginine, which does not affect cytochrome P-450 reductase. Dihydroergotamine, miconazole, and troleandomycin are classical inhibitors of cytochrome. The present study shows the concentration-dependent inhibitory effect of these compounds and of L- but not D-N-omega-nitro-arginine on the activity of constitutive nitric oxide synthase from bovine aortic endothelial cells. Activity of nitric oxide synthase was estimated by measurement of conversion of [3H]arginine to [3H]citrulline. The tested cytochrome P-450 inhibitors are likely to interfere with heme of nitric oxide synthase. The data confirms a similarity as well as functional differences between the enzymes.

Kinetics of binding of caldesmon to actin.

The time course of interaction of caldesmon with actin may be monitored by fluorescence changes that occur upon the binding of 12-(N-methyl-N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl))-labeled caldesmon to actin or to acrylodan actin. The concentration dependence of the observed rate of caldesmon-actin binding was analyzed to a first approximation as a single-step reaction using a Monte Carlo simulation. The derived association and dissociation rates were 10(7) M-1 s-1 and 18.2 s-1, respectively. Smooth muscle tropomyosin enhances the binding of caldesmon to actin, and this was found to be due to a reduction in the rate of dissociation to 6.3 s-1. There is no evidence from this study for a different mechanism of binding in the presence of tropomyosin. The fluorescence changes that occurred with the binding of 12-(N-methyl-N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl))-labeled caldesmon to actin or actin-tropomyosin were reversed by the addition of myosin subfragment 1 as predicted by a competitive binding mechanism.

Intracellular translocation of endothelial nitric oxide synthase by lysophosphatidylcholine.

The amphiphile lysophosphatidylcholine (LPC) modulates the activity of membrane-associated enzymes such as phospholipase A2, adenylate and guanylate cyclases and ATPase. LPC also relaxes vascular smooth muscle through production of nitric oxide. On the basis of reports that bradykinin translocates nitric oxide synthase (NOS) from the membrane to the cytosol, we investigated whether a similar translocation occurs with LPC. It was found that LPC translocated NOS from the membrane to the cytosolic fraction. Total NOS activity remained at the control level.

Immunohistochemistry in the identification of nitric oxide synthase isoenzymes in myocardial infarction.

OBJECTIVE: Inducible nitric oxide synthase (iNOS) activity, as measured by conversion of L-14C-arginine to L-14C-citrulline is significantly increased in infarcted rabbit myocardium as compared to healthy myocardium 48 h after coronary occlusion. The aim of this study was to localise the nitric oxide synthase (NOS) isoforms in normal myocardium and compare these findings with NOS activity in cells of the infarcted region. METHODS: Activities of NOS isoforms were enzymatically assayed in normal and infarcted myocardium. Localisation of NOS was performed on identical sections using specific monoclonal IgG antibodies against endothelial constitutive (cNOS) and macrophage inducible (iNOS) nitric oxide synthase. In addition, macrophages were identified using fluorescein conjugated ChromPure rabbit IgG, Fc fragment. RESULTS: iNOS activity increased significantly in infarcted as compared to normal myocardium [0.42(SEM 0.03) v 0.85(0.08) fmol.microgram-1.min-1, P = 0.02, respectively]. However, cNOS did not increase significantly in infarcted regions [0.18(0.04) v 0.24(0.06) fmol.microgram-1.min-1; P = 0.16, respectively]. cNOS was immunohistochemically localised in endothelial and endocardial cells in normal and infarcted tissues. The presence of iNOS activity in macrophages in infarcted myocardium was identified immunohistochemically. Cardiomyocytes and neutrophils did not label with the antibodies to cNOS and iNOS. CONCLUSIONS: (1) Infiltrating macrophages are the main site of increased iNOS activity in infarcted rabbit myocardium. (2) cNOS activity is not significantly increased in infarcted tissues as compared to normal myocardium. (3) Neutrophils and cardiomyocytes do not express NOS immunoreactivity in infarcted and normal rabbit myocardium.

Inducible nitric oxide synthase activity in myocardium after myocardial infarction in rabbit.

The activity of nitric oxide synthase (NOS) in infarcted and noninfarcted rabbit myocardium was determined. NOS activity, as measured by conversion of [14C]arginine to [14C]citrulline, was significantly higher in the infarcted area of myocardium (22.7 +/- 3.7 fmol/mg as compared to 7.67 +/- 1.0 in noninfarcted area). NOS activity within the area of risk remained on control level. Increased inducible NOS activity was observed on the first postoperative day and persisted for at least 14 days; it declined 3 weeks after infarction. Citrulline formation was inhibited by N-omega-nitro-L-arginine and N-omega-monomethyl-L-arginine The localization of NOS by monoclonal anti-NOS antibody indicates mononuclear cells/macrophages as the likely source of the enzyme. The concentrations of tumor necrosis factor-alpha and interleukin-1 beta were not increased in peripheral blood or myocardium.

Dexamethasone inhibits the expression of an inducible nitric oxide synthase in infarcted rabbit myocardium.

Infarcted areas of rabbit myocardium show relatively higher inducible nitric oxide synthase activity, measured by the conversion of L-[14C]arginine to L-[14C]citrulline. The principal finding in this study is that dexamethasone (2 mg/kg) prevents the induction of inducible nitric oxide synthase in heart muscle when given before, or even 3 hr after coronary artery ligation. Additionally cyclic GMP levels remain unchanged following treatment with dexamethasone. It is possible that the enhanced production of nitric oxide by inducible nitric oxide synthase accounts, at least in part, for the depression of myocardial contractility seen in myocardial infarction and in other clinical conditions.