Preservation of myocyte contractile function after hypothermic, hyperkalemic cardioplegic arrest with 2, 3-butanedione monoxime

One proposed contributory mechanism for depressed ventricular performance after hypothermic, hyperkalemic cardioplegic arrest is a reduction in myocyte contractile function caused by alterations in intracellular calcium homeostasis. Because 2,3-butanedione monoxime decreases intracellular calcium transients, this study tested the hypothesis that 2,3-butanedione monoxime supplementation of the hyperkalemic cardioplegic solution could preserve isolated myocyte contractile function after hypothermic, hyperkalemic cardioplegic arrest. Myocytes were isolated from the left ventricles of six pigs. Magnitude and velocity of myocyte shortening were measured after 2 hours of incubation under normothermic conditions (37 degrees C, standard medium), hypothermic, hyperkalemic cardioplegic arrest (4 degrees C in Ringer's solution with 20 mEq potassium chloride and 20 mmol/L 2,3-butanedione monoxime). Because beta-adrenergic agonists are commonly employed after cardioplegic arrest, myocyte contractile function was examined in the presence of the beta-agonist isoproterenol (25 nmol/L). Hypothermic, hyperkalemic cardioplegic arrest and rewarming reduced the velocity (32%) and percentage of myocyte shortening (27%, p < 0.05). Supplementation with 2,3 butanedione monoxime normalized myocyte contractile function after hypothermic, hyperkalemic cardioplegic arrest. Although beta-adrenergic stimulation significantly increased myocyte contractile function under normothermic conditions and after hypothermic, hyperkalemic cardioplegic arrest, contractile function of myocytes exposed to beta-agonist after hypothermic, hyperkalemic cardioplegic arrest remained significantly reduced relative to the normothermic control group. Supplementation with 2,3-butanedione monoxime restored beta-adrenergic responsiveness of myocytes after hypothermic, hyperkalemic cardioplegic arrest. Thus, supplementation of a hyperkalemic cardioplegic solution with 2,3-butanedione monoxime had direct and beneficial effects on myocyte contractile function and beta-adrenergic responsiveness after cardioplegic arrest. A potential mechanism for the effects of 2,3-butanedione monoxime includes modulation of intracellular calcium transients or alterations in sensitivity to calcium. Supplementation with 2,3-butanedione monoxime may have clinical utility in improving myocardial contractile function after hypothermic, hyperkalemic cardioplegic arrest.     

Retroviral display of antibody fragments; interdomain spacing strongly influences vector infectivity

Five different single-chain antibody fragments (scFv) against human cell-surface antigens were displayed on murine ecotropic retroviral vectors by fusing them to the Moloney SU envelope glycoprotein. The spacing between the scFv and the SU glycoprotein was varied by fusing the scFv to residue +7 or to residue +1 of Moloney SU and by inserting linker sequences of different lengths between the domains. All of the chimeric envelopes were efficiently incorporated into vector particles and could bind to human cells through their displayed antibody fragments, but did not infect them. The spacing between the scFvs and the SU glycoproteins had no significant effect on the efficiency of envelope expression or viral incorporation and did not affect the binding properties of the chimeric envelopes, nor did it influence the efficiency of targeted gene delivery to human cells by scFv-displaying vectors. However, on murine fibroblasts the infectivity of vectors incorporating the chimeric envelopes was strongly influenced by the length of the interdomain spacer. The titers were very low when the single-chain antibodies were fused through a tripeptide linker to SU residue +7 and were greatly enhanced (up to 10(5)-fold) when they were fused to SU residue +1 through a heptapeptide linker. These results point to the importance of steric interactions between the domains of chimeric envelope glycoproteins and may have implications for retroviral vector design for human gene therapy.     

Some pharmacologic and toxicologic studies on Rhazya stricta decne in rats, mice and rabbits

1. This work examines some in vivo and in vitro pharmacologic and toxicologic effects of extracts of Rhazya stricta, a medicinal plant in the United Arab Emirates. 2. R. stricta extracts at doses of 0.1-10 mg reduced the mean arterial blood pressure (MBP) of anesthetized rats in a dose-dependent manner. The depressor effect was partially sensitive to atropine (5 microM). Although the MBP was reduced by 50% by both doses of extracts, the normal electrocardiogram pattern and the heart rate remained unaltered. 3. Acute treatment of rats with the lyophilized extract at doses of 4 g/kg produced a significant rise in insulin concentration. In streptozotocin-diabetic rats loaded orally with glucose (1 g/kg), R. stricta at doses of 8 g/kg produced significant decreases in plasma glucose concentration at 0.5 and 1 h after treatment. 4. Chronic treatment of rats and mice for 28 days with the lyophilized extract of R. stricta did not affect the plasma glucose or insulin concentration or any of the hematological or biochemical indices measured. 5. The extracts of R. stricta (0.5-4 g/kg) dose-dependently decreased the gastrointestinal transit time in mice by 4-50%. 6. The butanolic extract of R. stricta (1 and 2 g/kg) significantly reduced the carrageenan-induced increase in raw paw edema 3 and 4 h after the extract administration. 7. The rectal temperatures of normothermic and pyrexic rats were reduced significantly 0.5 and 1 h after administration of butanolic R. stricta at doses of 1 and 2 g/kg. 8. The butanolic extract of R. stricta at doses of 1 and 2 g/kg significantly increased the reaction time on the hot plate 30 and 60 min after administration to rats. 9. At concentration < 0.05 mg/ml (bath concentration), lyophilized water and butanol extracts of R. stricta potentiated the twitch responses induced by indirect electrical stimulation in the rat phrenic nerve diaphragm preparation. The responses were inhibited by concentrations > 0.05 mg/ml. Neostigmine (2 x 10(-4)M) did not alter these effects of the extracts. 10. R. stricta extracts dose-dependently decreased the force of contraction and heart rate of the isolated rabbit heart. Atropine (1 x 10(-5)M) had no effect on the inhibitory activity of these extracts. The lyophilized water extract (> 10 mg) and butanol extract (> 5 mg) produced irreversible inhibition and disturbances in the force of contraction and heart rate.     

TiNi shape memory alloys prepared by normal sintering

This paper covers the use of conventional press and sinter of titanium and nickel equiatomic blends, involving transient liquid phases. A notable development has been the fabrication of homogeneous compacts from the elemental powders. Results indicate that employment of a double-stage sintering cycle is effective to sustain the geometrical integrity of the sintered sample. The TiNi alloy prepared in this manner exhibits a recovery strain of 4.6% by generating a restoring stress of 230 MPa, with a martensitic transformation point M_s of 34 °C.     

TEM and high-temperature X-ray diffractometric studies on the structural transformations in Ni3Al

High-temperature X-ray diffraction and TEM studies were conducted on nickel-rich boron-doped Ni₃Al in order to confirm our earlier observations on the existence of a structural transformation in these alloys. The results obtained are discussed through a model proposed. The L1₂ structure appears to transform to another L1₂ or to a DO₂₂ structure during heating. Such a transformation starts at around 700 °C and seems to complete around 1100 °C and appears to be of a continuous type. In the temperature range 700–1100 °C both phases coexist, which causes a tetragonal distortion of the L1₂ lattice giving rise to a tweed morphology in TEM observations. The transformation mechanism involves a periodic modulation of lattice constant. The calculated values for this periodicity (expressed as a number of unit cells in the [100] direction) obtained from X-ray diffraction (L = 62, 70, 74) matched well with that (L = 65) obtained using TEM.     

Envelope glycoprotein gp120 of human immunodeficiency virus type 1 alters ion transport in astrocytes: implications for AIDS dementia complex

Infection by human immunodeficiency virus type 1 (HIV-1) is often complicated by a variety of neurological abnormalities. The most common clinical syndrome, termed acquired immunodeficiency syndrome (AIDS) dementia complex, presents as a subcortical dementia with cognitive, motor, and behavioral disturbances and is unique to HIV-1 infection. The pathogenesis of this syndrome is poorly understood but is believed to involve interactions among virally infected macrophages/microglia, astrocytes, and neurons. In this study, we show that exposure of primary rat and human astrocytes to heat-activated HIV-1 virions, or to eukaryotically expressed HIV-1 and HIV-2 envelope glycoproteins (gp120) stimulates amiloride-sensitive Na+/H+ antiport, potassium conductance, and glutamate efflux. These effects are blocked specifically by amiloride, an inhibitor of Na+/H+ antiport and by the selective removal of gp120 with immobilized monoclonal antibody. As a result of modulation of astrocytic function by gp120, the ensuing neuronal depolarization and glutamate exposure could activate both voltage-gated and N-methyl-D-aspartate-regulated Ca2+ channels, leading to increases in intraneuronal Ca2+ and neuronal death. These findings implicate the astrocyte directly in the pathogenesis of AIDS dementia complex.     

A perioperative practicum

Complex rehabilitation of 20 patients with congenital and acquired maxillofacial deformations included psychological examinations using the finish-the-sentence test, Taylor's, Eysenck's [correction of Isenk's], Leonhard-Smisek, and Dembo-Rubinstein tests. Depressive states were detected in 4, neurotic reactions with depressive incorporations in 16 examinees. After surgery the manifestations of depression decreased in 60% of patients. Psychological studies helped improve the efficacy of surgery due to a favorable impact on the personality.     

A confocal microscopic evaluation of the effects of insulin imprinting on the binding of Concanavalin A by Tetrahymena Pyriformis

With confocal microscopy it is possible to study the Concanavalin A (Con A) binding characteristics of the surface and interior of a single cell by viewing optical sections. It was observed in Tetrahymena pyriformis that Con A bound both to the plasma membrane and to intracellular structures. Incubation of cells with a competing sugar a-methylmannopyranoside, decreased binding. Hormonal imprinting with insulin resulted in an increase in binding of Con A to the cell surface and a decrease in intracellular binding. It is possible that the intracellular binding sites may migrate to the plasma membrane.     

Correlative MR-anatomic study of the median nerve

OBJECTIVE: The purpose of our study was to evaluate the effectiveness of MR imaging for showing the intrinsic anatomy of a peripheral nerve. Cadaver wrist specimens that included the median nerve were imaged with MR imaging at 3 T, then sectioned, stained, and inspected grossly and microscopically. The size, shape, and signal intensity of the sheath and axonal structures in the median nerve were identified in MR images by comparison with anatomic sections. CONCLUSION: This study suggests that MR imaging with sufficiently high-resolution techniques shows the internal structure of peripheral nerves. These results suggest that MR imaging may be a means to distinguish neuritis, tumor, degeneration, or fatty proliferation in a peripheral nerve and to evaluate the nerve before microsurgical anastomosis.