Effect of single oral dose of azithromycin, clarithromycin, and roxithromycin on polymorphonuclear leukocyte function assessed ex vivo by flow cytometry

Azithromycin was given as a single oral dose (20 mg/kg of body weight) to 12 volunteers in a crossover study with roxithromycin (8 to 12 mg/kg) and clarithromycin (8 to 12 mg/kg). Flow cytometry was used to study the phagocytic functions and the release of reactive oxygen products following phagocytosis by neutrophil granulocytes prior to administration of the three drugs, 16 h after azithromycin administration, and 3 h after clarithromycin and roxithromycin administration. Phagocytic capacity was assessed by measuring the uptake of fluorescein isothiocyanate-labeled bacteria. Reactive oxygen generation after phagocytosis of unlabeled bacteria was estimated by the amount of dihydrorhodamine 123 converted to rhodamine 123 intracellularly. Azithromycin resulted in decreased capacities of the cells to phagocytize Escherichia coli (median [range], 62% [27 to 91%] of the control values; P < 0.01) and generate reactive oxygen products (75% [34 to 26%] of the control values; P < 0.01). Clarithromycin resulted in reduced phagocytosis (82% [75 to 98%] of control values; P < 0.01) but did not alter reactive oxygen production (84% [63 to 113%] of the control values; P > 0.05). Roxithromycin treatment did not affect granulocyte phagocytosis (92% [62 to 118%] of the control values; P > 0.05) or reactive oxygen production (94% [66 to 128%] of the control value; P > 0.05). No relation between intra- and/or extracellular concentrations of azithromycin and/or roxithromycin and the polymorphonuclear phagocyte function and/or reactive oxygen production existed (P > 0.05 for all comparisons). These results demonstrate that the accumulation of macrolides in neutrophils can suppress the response of phagocytic cells to bacterial pathogens after a therapeutic dose.     

A novel metal-insulator-metal structure for field-programmabledevices

A metal-insulator-metal (MIM) capacitor structure has been developed for use in field-programmable gate arrays (FPGAs) as a voltage-programmable link (VPL). The structure relies on a combination of a refractory metal and aluminum as the lower electrode, and either a similar combination or aluminum alone as the top electrode. The insulator is prepared by means of plasma-enhanced chemical vapor deposition (PECVD). It comprises a sandwich of nearly stoichiometric silicon dioxide interposed between two like layers of silicon-rich silicon nitride. The structure has displayed characteristics desirable for use in emerging FPGA technology, including high density, low on-resistance, reduced capacitance, and low programming voltage     

Peritoneal healing after fibrin glue application: a comparative study in a rat model

The influence of fibrin glue on adhesion formation and peritoneal healing is evaluated in a prospective, randomized, controlled study. In all, 20 Wistar rats underwent microsurgical suturing of two silicone sheets, one covered with a fibrin glue barrier, to the anterior peritoneum. Each animal thus served as its own control. After 10 days, adhesions and peritoneal healing were evaluated by a blinded observer through a second-look laparotomy. Adhesions were scored using a modification of the classification of Diamond. Tissue around the silicone sheet was examined histologically and by scanning electron microscopy to evaluate the inflammatory reaction and peritoneal healing (ingrowth of blood vessels and quality of peritoneal cells). Adhesion scores for treated and control sides were (mean +/- SD) 2.89 +/- 4.68 and 6.79 +/- 9.09 (P = 0.181) respectively, and the percentage of the sheet covered by peritoneum was 26.25 +/- 31.50 and 29.21 +/- 40.21 (P = 0.226) respectively. Using the paired Wilcoxon rank test, the P values for the ingrowth of blood vessels and peritoneal healing evaluated by histology and scanning electron microscopy were 0.842, 0.692 and 0.695 respectively. We conclude that although the mean adhesion score was reduced by > 50% by fibrin glue, there is no statistically significant difference concerning adhesion formation or peritoneal healing with the use of fibrin glue.     

Characterization of spherically focused transducers using an ultrasonic measurement model approach

A new and computationally efficient method is developed for characterizing a spherically focused, ultrasonic transducer (and its accompanying test system). Procedures for determining the probe's effective radius, effective focal length, and system efficiency factor are described. Predicted responses that make use of these effective parameters are shown to correspond very well to measured responses for a number of different transducers.     

Beam test of the CsI(Tl) calorimeter for the BELLE detector at the KEK-B factory

We studied the performance of a prototype electromagnetic calorimeter for the BELLE detector at the KEK proton synchrotron for an energy range of 0.25–3.5 GeV. The prototype consisted of an array of 6 × 5 CsI(Tl) crystals with 30 cm length (16.2 radiation lengths) and about 6 cm × 6 cm cross section. The scintillation light of each CsI(Tl) crystal was read out by two large-area PIN photodiodes and charge-sensitive preamplifiers attached at the rear face of the crystal. We measured the energy and position resolution for electrons and the e/π separation for two sets of matrix configurations: one corresponded to the center and the other to the edge of the barrel calorimeter. The overall performance measured by the test proves that the prototype calorimeter is satisfactory for the use in the BELLE detector.     

Large purely refractive nonlinear index of single crystal P-toluenesulphonate (PTS) at 1600 nm

Z-scan measurements at 1600 nm on single-crystal PTS (p-toluene sulfonate) with single, 65 ps pulses gave a complex nonlinear refractive index coefficient of n₂=2.2(±0.3)×10^-12 cm²/W at 1 GW/cm² and α₂<0.5 cm/GW. This is the first highly nonlinear, organic material to satisfy the conditions imposed by the figures of merit     

Two mechanisms for the recapture of extracellular GM2 activator protein: evidence for a major secretory form of the protein

The GM2 activator protein is a small monomeric protein containing a single site for Asn-linked glycosylation. Its only proven in vivo function is to act as a substrate specific cofactor for the hydrolysis of GM2 ganglioside by lysosomal beta-hexosaminidase A. However, we and others have shown it can act as a general glycolipid transporter at neutral pH in vitro. Any other possible in vivo functions would require that some of the newly synthesized activator molecules not be targeted to the lysosome. The lysosomal targeting mechanism for the activator has not been conclusively identified. While earlier reports suggested that it is likely through the mannose-6-phosphate receptor, another more recent report demonstrated that deficient human cells could recapture nonglycosylated, bacterially produced activator, suggesting its use of an alternate targeting pathway. Here, we demonstrate that the mannose-6-phosphate pathway is likely the major intracellular, biosynthetic route to the lysosome, as well as a high affinity recapture pathway for the endocytosis of activator protein from extracellular fluids. Additionally, we show that there exists a second lower affinity recapture pathway that requires its native protein structure, is carbohydrate independent, and likely does not involve its ability to bind glycosphingolipids in the plasma membrane. Finally, we document that the pool of newly synthesized precursor activator protein contains a majority of molecules with a complex-type oligosaccharide, which cannot contain a functional mannose-6-phosphate targeting signal. These molecules makeup the secreted forms of the protein in normal human fibroblasts.     

The viscosity of liquid water at pressures up to 32 MPa

The paper reports new, preliminary measurements of the viscosity of liquid water along two isotherms as a function of pressure up to 32 MPa. The measurements have been performed with a vibrating-wire viscometer especially modified for the purpose. The instrument has been calibrated with respect to the viscosity of water at a pressure of 0.1 MPa and a temperature of 293.15 K, for which an accurate reference value is available. With due regard to the precision of the determination of individual quantities and the accuracy of the calibration data, it is estimated that the accuracy of the present results is one of ±0.3% under all conditions.Paper dedicated to Professor Joseph Kestin.     

The effects of retinol on in vitro immunoglobulin synthesis by cord blood and adult peripheral blood mononuclear cells

In this study we examined the effects of retinol (ROH), a metabolic precursor of retinoic acid (RA), on Staphylococcus aureus Cowan I (SAC)-induced immunoglobulin synthesis of cord blood mononuclear cells (CBMC) and adult peripheral blood mononuclear cells (PBMC). ROH augmented SAC-induced IgM synthesis of CBMC by 5.9 +/- 1.5-fold (n = 7, mean +/- s.d.), and IgG synthesis of adult PBMC by 16.3 +/- 5.1-fold (n = 3) at optimal concentrations of 10(-6) M and 10(-11) M, respectively. No augmenting effects could be demonstrated for the other immunoglobulin isotypes. Time-course studies showed that the synthesis of IgM by CBMC was accelerated with detectable immunoglobulin in supernatant fluids starting on day 3. ROH augmented immunoglobulin synthesis of CBMC stimulated by Epstein-Barr virus (EBV), a T cell-independent polyclonal activator, and of EBV-transformed B cell clones (2.5 +/- 0.2 and 4.1 +/- 1.5-fold increase, respectively), which suggests that ROH can act directly on B cells to enhance immunoglobulin synthesis. In contrast, when ROH was preincubated with cord blood T cells, washed and added to the B cell-enriched fraction with SAC, no increase (0.9-1.8-fold) in IgM synthesis was obtained. Thus, the principal mechanism(s) by which ROH augments immunoglobulin synthesis is by acting on B cells. This is in contrast to the immunoglobulin-enhancing effects of RA which is mediated by T cells, or T cell products, e.g. cytokine. Our studies suggest that RA and ROH may have different pathways of immunoglobulin-enhancing effects, perhaps mediated by different retinoid binding proteins resulting in gene activation and immunoglobulin synthesis.