Reduction by cefodizime of the pulmonary inflammatory response induced by heat-killed Streptococcus pneumoniae in mice

It has recently become apparent that overwhelming inflammatory reactions contribute to the high mortality rate associated with pneumococcal infection in immunocompetent hosts. Cefodizime (CEF) is an antibiotic that seems to be endowed with immunomodulating properties. To investigate the influence of CEF on the pulmonary inflammatory response induced by Streptococcus pneumoniae, we infected mice with repeated intranasal inoculations of 10(7) CFU of heat-killed fluorescein isothiocyanate-labeled bacteria, which are insensitive to the killing properties of the drug. CEF downregulated but did not abolish the strong polymorphonuclear leukocyte (PMN) recruitment induced by S. pneumoniae. PMN recruitment was not primarily mediated by leukotriene B4 in this model. The drug did not interfere with intrinsic mechanisms of phagocytosis by PMNs and alveolar macrophages. CEF totally abrogated the pneumococcus-induced tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) secretion in bronchoalveolar lavage fluid. The drug also prevented IL-6 release in lung homogenates and partly inhibited TNF-alpha, but it did not interfere with IL-1alpha secretion in the lungs of infected mice. The fractional and selective downregulation of inflammatory cells and cytokines by CEF suggests cell-specific and intracellular specific mechanisms of interaction of the drug. The immunomodulatory properties of CEF may help restrain excessive inflammatory reactions, thus contributing to the reported good clinical efficacy of the drug against lower respiratory tract infections.     

Aspects of poly(p-phenylene sulfide) degradation and stabilization. Part 1. Influence of polymer end groups on exposure induced coloration

In this paper we reviewed some of our work on the photo induced coloration of Poly(p-phenylene sulfide) (PPS) and compared it to recent results obtained from the thermal treatment of resins that varied in molecular weight and ionic content. The results from this study suggest that coloration of amorphous PPS films after UV irradiation is caused by products different from those that cause coloration in semicrystalline PPS after thermoxidation. In addition, we found that polymer end group chemistry and resin molecular weights play important roles in the thermoxidative coloration of PPS, but only nominally influence the photooxidative coloration of the resin. PPS coloration may arise from the accumulation of specific, colored products (e.g., phenyl-phenyl moieties) and the possible presence of intermolecular aggregates. The mechanism and extent by which these structures occur in UV irradiated or heated PPS are likely dependent upon the polymer morphology of the samples tested.     

Magnesium enhances function of postischaemic human myocardial tissue

OBJECTIVES: The effect of Mg2+ on the developed force and concentrations of high energy phosphate metabolites in isolated human atrial trabeculae has been investigated. METHODS: Human atrial trabeculae, obtained from right atrial appendages of patients undergoing cardiac surgery requiring cardiopulmonary bypass, were dissected at room temperature in modified Krebs-Henseleit buffer containing 1.2 or 16 mM Mg2+, mounted on muscle stands, and rewarmed to 34 degrees C in the same buffer. After 30 minutes, their mechanical function was assessed. At the end of the protocol, trabeculae were fast frozen for measurement of concentrations of metabolites of high energy phosphates. RESULTS: Trabeculae collected and rewarmed in 16 mM Mg2+ Krebs-Henseleit buffer showed significantly higher mean developed force (0.59(SEM 0.10) g, p < 0.01) than those rewarmed in 1.2 mM Mg2+ Krebs-Henseleit buffer (0.32(0.03) g). Trabeculae that had a developed force > or = 0.8 g, a resting force < or = 0.7 g, and a cross sectional area < or = 1 mm2 ("functional" trabeculae) were selected for further comparison. New reverse phase high performance liquid chromatography techniques developed for the analysis of small samples (0.5-5 mg dry weight) were used to measure nucleotide, nucleoside, and creatine compounds. Total adenylate (ATP+ADP+AMP) concentrations in trabeculae revived in the presence of 16 mM Mg2+ (15.4(1.1) mumol.g-1 dry weight) were significantly higher (p < 0.01) than in those revived with 1.2 mM Mg2+ (11.8(1.0) mumol.g-1), but lower (p < 0.01) than in trabeculae fast frozen immediately after removal from the patient (22.6(1.0) mumol.g-1). There were no significant differences in NAD and total creatine (phosphocreatine+creatine) concentrations between the three groups. CONCLUSIONS: The presence of high Mg2+ during the rewarming of human atrial trabecular preparations maintains a significantly higher developed force and a significantly higher total adenylate pool than does collection and rewarming with normal concentrations of Mg2+.     

Picture naming of cognate and non-cognate nouns in bilingual aphasia

Previous research has found differences in the speed and accuracy of responses involving concrete cognate nouns and non-cognate nouns in a range of written and "on-line" tasks using neurologically unimpaired, bilingual adults. The present study investigated whether cognateness affects verbal confrontation naming performance in balanced French/English bilinguals (N = 15 aphasic and 15 non-aphasic subjects). Subjects met selection criteria for equal proficiency, regular use, and early acquisition of both languages. Results of a picture naming test show that cognate pictures were more often correctly named in both languages than were non-cognates. Some error types and self-correction behaviors also varied with cognate status. There were similarities between the results of this study and those of previous studies of monolingual naming. Some error types and self-correction strategies appear to be unique to bilingual speakers. Theoretical questions and treatment applications arising from these findings are outlined.     

An in vitro tissue culture bilayer model to examine early events in Mycobacterium tuberculosis infection

A tissue culture bilayer system that mimics some aspects of early alveolar infection by Mycobacterium tuberculosis was developed. This model incorporates human lung epithelial type II pneumocyte (A549) (upper chamber) and endothelial cell (lower chamber) layers separated by a microporous membrane. This construction makes it possible to observe and quantify the passage of bacteria through the two layers, to observe the interaction of the bacteria with the various cell types, and to examine the basic mechanisms of immune cell recruitment to the site of infection. After 10(7) organisms were added to the upper chamber we microscopically observed large numbers of bacteria attached to and within the pneumocytes and we determined by viable-cell counting that a small percentage of the inoculum (0.02 to 0.43%) passed through the bilayer into the lower chamber. When peripheral blood mononuclear cells were added to the lower chamber, microscopic examination indicated a migration of the mononuclear cells through the bilayer to the apical surface, where they were seen associated with the mycobacteria on the pneumocytes. The added complexity of the bilayer system offers an opportunity to define more precisely the roles of the various lung cell types in the pathogenesis of early tuberculosis.     

Evaluation of cardiac 31P magnetic resonance spectroscopy: reviewing NMR principles

Methylguanidine, guanidinoacetic acid and guanidinosuccinic acid are endogenous substances in body tissues. Extremely high levels of these substances are known to be related to the pathogenesis of epilepsy and renal failure such as uremia. In this study it was demonstrated that methylguanidine, guanidinoacetic acid and guanidinosuccinic acid, and arginine generate hydroxyl radicals in aqueous solution. These findings suggest that a high level of guanidino compounds accumulating near or within cells such as neurons (in an epileptogenic focus) or nephrons (in uremic patients) may cause free radical damage leading to these clinical disorders. Arginine may have a similar role in the pathogenesis of hyperarginemia.     

Dynamics of Antimonene–Graphene Van Der Waals Growth

Van der Waals (vdW) heterostructures have recently been introduced as versatile building blocks for a variety of novel nanoscale and quantum technologies. Harnessing the unique properties of these heterostructures requires a deep understanding of the involved interfacial interactions and a meticulous control of the growth of 2D materials on weakly interacting surfaces. Although several epitaxial vdW heterostructures have been achieved experimentally, the mechanisms governing their synthesis are still nebulous. With this perspective, herein, the growth dynamics of antimonene on graphene are investigated in real time. In situ low‐energy electron microscopy reveals that nucleation predominantly occurs on 3D nuclei followed by a self‐limiting lateral growth with morphology sensitive to the deposition rate. Large 2D layers are observed at high deposition rates, whereas lower growth rates trigger an increased multilayer nucleation at the edges as they become aligned with the Z2 orientation leading to atoll‐like islands with thicker, well‐defined bands. This complexity of the vdW growth is elucidated based on the interplay between the growth rate, surface diffusion, and edges orientation. This understanding lays the groundwork for a better control of the growth of vdW heterostructures, which is critical to their large‐scale integration.     

Pathways of Rb+ influx and their relation to intracellular [Na+] in the perfused rat heart. A 87Rb and 23Na NMR study

The aims of this study were to characterize the routes of influx of the K+ congener, Rb+, into cardiac cells in the perfused rat heart and to evaluate their links to the intracellular Na+ concentration ([Na+]i) using 87Rb and 23Na nuclear magnetic resonance (NMR) spectroscopy. The rate constant for Rb+ equilibration in the extracellular space was 8.5 times higher than that for the intracellular space. The sensitivity of the rate of Rb+ accumulation in the intracellular space of the perfused rat heart to the inhibitors of the K+ and Na+ transport systems has been analyzed. The Rb+ influx rates were measured in both beating and arrested hearts: both procaine (5 mmol/L) and lidocaine (1 mmol/L) halved the Rb+ influx rate. In procaine-arrested hearts, the Na+,K(+)-ATPase inhibitor ouabain (0.6 mmol/L) decreased Rb+ influx by 76 +/- 24% relative to that observed in untreated but arrested hearts. Rb+ uptake was insensitive to the K+ channel blocker 4-aminopyridine (1 mmol/L). The inhibitor of Na+/K+/2 Cl- cotransport bumetanide (30 mumol/L) decreased Rb+ uptake only slightly (by 9 +/- 8%). Rb+ uptake was dependent on [Na+]i: it increased by 58 +/- 34% when [Na+]i was increased with the Na+ ionophore monensin (1 mumol/L) and decreased by 48 +/- 9% when [Na+]i was decreased by the Na+ channel blockers procaine and lidocaine. Dimethylamiloride (15 to 20 mumol/L), an inhibitor of the Na+/H+ exchanger, slightly reduced [Na+]i and Rb+ entry into the cardiomyocytes (by 15 +/- 5%). 31P NMR spectroscopy was used to monitor the energetic state and intracellular pH (pHi) in a parallel series of hearts. Treatment of the hearts with lidocaine, 4-aminopyridine, dimethylamiloride, or bumetanide for 15 to 20 minutes at the same concentrations as used for the Rb+ and Na+ experiments did not markedly affect the levels of the phosphate metabolites or pHi. These data show that under normal physiological conditions, Rb+ influx occurs mainly through Na+,K(+)-ATPase; the contribution of the Na+/K+/2 Cl- cotransporter and K+ channels to Rb+ influx is small. The correlation between Rb+ influx and [Na+bdi during infusion of drugs that affect [Na+]i indicates that, in rat hearts at 37 degrees C, Rb+ influx can serve as a measure of Na+ influx. We estimate that, at normothermia, at least 50% of the Na+ entry into beating cardiac cells is provided by the Na+ channels, with only minor contributions (< 15%) from the Na+/K+/2 Cl- cotransporter and the Na+/H+ exchanger.