Preventing oxygen free-radical injury in ischemic revascularized bone grafts

Superoxide radicals have been shown to play a role in the cellular injury of reperfused ischemic tissues. We examined the protective effect of superoxide dismutase (SOD), a superoxide radical scavenger, on the reperfusion injury of replanted vascularized bone grafts after 4- and 8-hour periods of ischemia in a rat model. Histologic, fluorochrome, and histomorphometric analyses showed no difference between 4-hour superoxide dismutase-treated and control grafts, with both groups appearing viable. Similar analyses of the 8-hour ischemic grafts revealed both a qualitative and statistically significant quantitative difference (p less than 0.001) between the superoxide dismutase-treated and control grafts in parameters related to viability. Our results indicated that the administration of superoxide dismutase to free vascularized grafts by means of intraarterial perfusion after prolonged periods of warm ischemia significantly enhances the survival of these grafts.     

Differences in steroidogenesis by the subcellular fractions of adrenocortical special zone and cortex proper of the female possum (Trichosurus vulpecula)

Steroidogenesis by subcellular fractions of adrenal cortex proper (C.P.) and special zone (S.Z.) of female possum (Trichosurus vulpecula) was studied. Mitochondrial, microsomal and cytosol cell fractions were incubated with appropriate substrates in the presence of an NADPH-generating system. The major products formed from [3H]progesterone and [3H]17 alpha-hydroxyprogesterone by the microsomal fraction of the C.P. were 11-deoxycortisol and 11-deoxycorticosterone and 3 alpha (beta)-hydroxy-5 alpha-androstan-17-one by the S.Z. The mitochondrial fraction converted [3H]11-deoxycortisol to cortisol in yields twenty times higher by the C.P. than by the S.Z. and to 17 alpha, 20 beta,21-trihydroxy-4-pregn-3-one thirty times higher by the S.Z. The conversion of [3H]androstenedione to 11 beta-hydroxyandrostenedione by the C.P. was approximately double that of the S.Z., while 18-hydroxyandrostenedione (tentatively identified) formed the highest yield in both zones. Incubation of the same substrates with cytosol formed two 5 beta-pregnane and two 5 beta-androstane derivatives in total yields less than 5% by C.P. and greater than 60% by S.Z. Aromatase activity, estimated by the release of [3H2O] from [1 beta 3H]testosterone, in the adrenals of 8 possums, was in each experiment negligibly low. Determination of total enzyme activities in the two zones revealed that 11 beta, 18 and 21-hydroxylases were higher in the C.P., while 17 alpha-hydroxylase was higher in the S.Z. Similar results were obtained when the rates of formation of hydroxylated products were estimated in the presence of saturating amounts of substrates. Active 5 alpha- and 5 beta-reductases, C17-20-lyase and 3 alpha (beta) and 20 beta-hydroxysteroid dehydrogenases were found almost exclusively in the S.Z. We conclude that the S.Z. at lower levels of activity than the C.P. could contribute to the basal secretion of corticosteroids. In addition, the S.Z. has a high capacity to form C19 steroids and 5 alpha- and 5 beta-reduced steroids. The possible role of the S.Z. in possum is discussed.     

Effect of inspired air temperature on genioglossus activity during nose breathing in awake humans

Experimental data suggest the presence of sensory receptors specific to the nasopharynx that may reflexly influence respiratory activity. To investigate the effects of inspired air temperature on upper airway dilator muscle activity during nose breathing, we compared phasic genioglossus electromyograms (EMGgg) in eight normal awake adults breathing cold dry or warm humidified air through the nose. EMGgg was measured with peroral bipolar electrodes during successive trials of cold air (less than or equal to 15 degrees C) and warm air (greater than or equal to 34 degrees C) nasal breathing and quantified for each condition as percent activity at baseline (room temperature). In four of the subjects, the protocol was repeated after topical nasal anesthesia. For all eight subjects, mean EMGgg was greater during cold air breathing than during baseline (P less than 0.005) or warm air breathing (P less than 0.01); mean EMGgg during warm air breathing was not significantly changed from baseline. Nasal anesthesia significantly decreased the mean EMGgg response to cold air breathing. Nasal airway inspiratory resistance, measured by posterior rhinomanometry in six subjects under similar conditions, was no different for cold or warm air nose breathing [cold 1.4 +/- 0.7 vs. warm 1.4 +/- 1.1 (SD) cmH2O.l-1.s at 0.4 l/s flow]. These data suggest the presence of superficially located nasal cold receptors that may reflexly influence upper airway dilating muscle activity independently of pressure changes in awake normal humans.     

Recent Trends in the Management of Life-Threatening Ventricular Arrhythmias

An edited summary of an Interdepartmental Conference arranged by the Department of Medicine, UCLA School of Medicine, Los Angeles. William M. Pardridge, MD, Associate Professor of Medicine, is Director of Conferences.This study was supported in part by grants from the Public Health Service; the National Institutes of Health (HL-23970, 1978-1981); the Medical Research Service of the Veterans Administration, and the American Heart Association, the Greater Los Angeles Affiliate.     

Relationship Between Molecular Structure and Thermo-mechanical Properties of Candelilla Wax and Amides Derived from (<Emphasis Type="Italic">R</Emphasis>)-12-Hydroxystearic Acid as Gelators of Safflower Oil

In this research, we studied the relationship between the molecular structure of (R)-12-hydroxyoctadecanamide, (R)-N-propyl-12-hydroxyoctadecanamide, and (R)-N-octadecyl-12-hydroxyoctadecanamide and the thermo-mechanical properties of their 2% (wt/wt) organogels developed using safflower oil high in oleic acid (HOSFO) as the liquid phase. Candelilla wax (CW), a well-known edible gelling additive whose main component is hentriacontane, also was studied for comparative purposes. The results obtained show that the attractive interactions (i.e., hydrogen bonding and dipolar interactions) between amide groups and between hydroxyl groups present in the amides resulted in organogels with higher melting temperature, heat of melting, and crystallization parameters than those found in the CW organogel. The rheological parameters associated to the strength of the amide or CW-based gels developed in HOSFO (i.e., yield stress and elastic modulus) seem to be associated with the nature of amide groups (i.e., primary or secondary amide) and the increase in the length of the self-assembly molecular unit (i.e., L value determined by X-ray diffraction) and therefore to the extent of London dispersion forces along the hydrocarbon chain. The creep and recovery measurements allowed an evaluation among the internal structures of the different organogels and demonstrated that independent of the hydrogen bonding and dipolar interaction provided by the amide and the hydroxyl groups, the increase in the hydrocarbon chain length results in higher organogel resistance to deformation and higher instant recovery capacity. However, the stabilization of the self-assembly unit through polar groups (i.e., –CONH₂ in HOA) reduces organogel elasticity but provides a higher extended recovery capacity. The results reported in this investigation showed some relationships between gelator structure and the thermo-mechanical properties of low-molecular-mass organic gelator amides. Our long-term objective is to understand the organogelation process to eventually develop trans-free vegetable oil-based food products with novel textures for the consumers.     

Get the News Out Loudly and Quickly: The Influence of the Media on Limiting Emerging Infectious Disease Outbreaks

During outbreaks of infectious diseases with high morbidity and mortality, individuals closely follow media reports of the outbreak. Many will attempt to minimize contacts with other individuals in order to protect themselves from infection and possibly death. This process is called social distancing. Social distancing strategies include restricting socializing and travel, and using barrier protections. We use modeling to show that for short-term outbreaks, social distancing can have a large influence on reducing outbreak morbidity and mortality. In particular, public health agencies working together with the media can significantly reduce the severity of an outbreak by providing timely accounts of new infections and deaths. Our models show that the most effective strategy to reduce infections is to provide this information as early as possible, though providing it well into the course of the outbreak can still have a significant effect. However, our models for long-term outbreaks indicate that reporting historic infection data can result in more infections than with no reporting at all. We examine three types of media influence and we illustrate the media influence with a simulated outbreak of a generic emerging infectious disease in a small city. Social distancing can never be complete; however, for a spectrum of outbreaks, we show that leaving isolation (stopping applying social distancing measures) for up to 4 hours each day has modest effect on the overall morbidity and mortality.     

Protein kinase C (PKC) level is increased in PC12 cells overexpressing transfected liver-type phosphofructokinase

Summary— PC12 cells which overexpress transfected liver-type phosphofructokinase (PFKL) have previously been described as a model system for PFKL overexpression in Down's syndrome and have been shown to perform glycolysis at enhanced rates. Here we report that levels of protein kinase C (PKC) in PC 12-PFKL cells were almost doubled, as estimated from in vitro activity and phorbol ester binding experiments and from an increase found in PKC-alpha mRNA levels. Most of the added PKC was found to be associated with the cellular membrane while the cytoplasmic levels of PKC were barely increased. The steady-state levels of 1,2-sn-diacylglycerol in PC12-PFKL cells were found to be unaltered, suggesting that enhanced glycolysis in these cells did not influence PKC by altering the amounts of this compound. PFKL is one of several genes known to be overexpressed in Down's syndrome. Upregulation of PKC due to PFKL overexpression could result in widespread disturbances of gene expression and play a part in causing some of the many symptoms of the disease.     

Some electrical properties of the surfaces of murine B- and T-lymphocytes and thymocytes. II. Effects of neuraminidase and ribonuclease.

The electrical properties of the peripheries of murine thymocytes, B-lymphocytes and T-lymphocytes were studied by measurement of electrophoretic mobilities and electron microscopic quantitation of adsorbed, positively charged CIH particles. The effects of neuraminidase and/or ribonuclease treatment upon these parameters were examined. Neuraminidase-susceptible groups accounted for 17%, 13% and 21% of the net surface negativity of T-lymphocytes, B-lymphocytes and thymocytes, respectively, and 28%, 63% and 78% respectively of particle binding. The calculated numbers of charges at the cellular electrokinetic surface per observed CIH particle were similar in control T-cells and thymocytes and higher than in B-lymphocytes. In neuraminidase-treated T- and B-lymphocytes the calculated charges per CIH particle were much lower than in thymocytes. These results may well indicate heterogeneities in the distribution of groups susceptible to neuraminidase, and also in the distribution and/or chemical nature of anionic groups susceptible to neither neuraminidase nor ribonuclease at the peripheries of different murine lymphocyte populations; however, at present we cannot discriminate between these and other possibilities.