We studied the luminol-amplified chemiluminescence (CL) response of human polymorphonuclear leukocytes (PMNLs) stimulated with synthetic monosodium urate monohydrate (MSUM) crystals. Stimulation of PMNLs prepared from healthy controls with MSUM resulted in a bimodal CL response with two peaks after 1 min and 4-6 min, respectively. MSUM caused neutrophils to produce reactive oxygen species (ROS), which are released from the cells as well as ROS with an intracellular localization. Proportionally more of the CL activity generated during the first peak was of extracellular origin. The MSUM-induced light-generating mechanism was azide-sensitive, required superoxide anion and was strongly suppressed by horseradish peroxidase.

Ascorbic Acid↗

PubMedDate not supplied

In vitro activity of lomefloxacin (NY-198 or SC 47111).

The activity of lomefloxacin was compared to that of four other quinolones. Minimum inhibitory concentrations (MICs) were similar to those of enoxacin, norfloxacin, and ofloxacin against the Enterobacteriaceae, Pseudomonas aeruginosa, Staphylococcus spp. and Enterococcus faecalis. The activity of lomefloxacin was antagonized in urine at pH 5.4, but not in urine at pH 7.0. Higher inocula required higher lomefloxacin concentrations for inhibition. Lomefloxacin was more active at alkaline pH. At concentrations equal to or 2-fold the MIC, it was rapidly bactericidal against Gram-negative organisms and required a longer time for the reduction of inoculum by 99% and 99.9%. An "Eagle effect" was seen against Escherichia coli and Staphylococcus aureus but not against P. aeruginosa.

4-Quinolones↗

PubMedDate not supplied

Effect of cytokines and lipopolysaccharides on HIV infection of human macrophages.

Human blood-borne monocytes (MO) differentiating into mature macrophages (MAC) were cultured on hydrophobic Teflon membranes. The cells were infected with two different monocytotropic HIV isolates: HIV1D117III obtained from a perinatally infected child, and HIV2D194 obtained from an AIDS patient who suffered exclusively from neurological symptoms. Virus production monitored by reverse transcriptase activity and HIV-antigen ELISA in cell-free supernatant was of a high level and continued for several weeks. To investigate possible modulatory pathways interfering with HIV infection in MAC we tested various recombinant cytokines as well as bacterial lipopolysaccharides (LPS) in our culture system. Whereas interleukin-1 (IL1) accelerated and increased HIV replication in MO/MAC, the interferons (IFN) alpha, beta and gamma effectively suppressed or delayed infection depending on the concentration used. Suppression was seen at concentrations as low as 0.3 U/ml and was most effective when the IFN were given prior to infection. No effect was observed with IL6 up to 2,000 U/ml. LPS affected virus infection in a complex manner: at 1-100 ng/ml virus replication was inhibited, but it was enhanced at subnanogram concentrations (25-100 pg/ml).

Cytokines↗

PubMedDate not supplied

Pentosidine and N(epsilon)-(carboxymethyl)-lysine in Alzheimer's disease and vascular dementia.

Increasing evidence suggests an interaction of oxidative stress and the formation of advanced glycation end products (AGE) in the onset and progression of Alzheimer's disease. We studied levels of pentosidine and N(epsilon)-(carboxymethyl)-lysine (CML) in serum and cerebrospinal fluid (CSF) of 15 patients with probable Alzheimer's disease (AD), 20 patients with vascular dementia (VD), and 31 control subjects (14 matched for age, and 17 younger patients). AGE protein concentrations in CSF did not differ within controls when divided into two subgroups by age. We found significantly elevated levels of CML in CSF of AD patients and of pentosidine in CSF of patients suffering from vascular dementia when compared to controls. The concentrations of pentosidine and CML in serum apparently did not relate directly to CSF values, suggesting influence of extra-cerebral factors in serum samples. It is concluded that AGE proteins are differentially affected in these types of dementia, depending on the specific neuropathology. Furthermore, measurements of AGE products in vivo should rely on CSF rather than blood samples.

Aged↗

PubMedDate not supplied

Harmonisation of rat fetal skeletal terminology and classification. Report of the Third Workshop on the Terminology in Developmental Toxicology. Berlin, 14-16 September 2000.

The initial efforts of the Federal Institute for Health Protection of Consumers and Veterinary Medicine (BgVV) and the Free University of Berlin to standardise terminology in the field of developmental toxicology began in 1995. Procedures were undertaken to harmonise the terminology used by the International Federation of Teratology Societies (IFTS) and the International Programme on Chemical Safety (IPCS). This article reflects these activities and is a report on the Third Workshop on the Terminology in Developmental Toxicology held in September 2000. This Workshop served as a forum to discuss the results of a survey on the classification of skeletal anomalies that had been previously sent to scientists active in the field. Although high agreement was reached among the evaluators for several terms, the use of a number of terms was rather variable. Therefore, the discussions at the workshop among the experts from research institutions, regulatory agencies, and industry were mainly focussed on those terms for which there was disagreement and/or uncertainties and the possible reasons. Pictures provided by the participants for the illustration of "grey zone" anomalies constituted the basis for detailed discussions. In many of the cases with lower agreement, decisions were facilitated by the provision of the corresponding picture. The main reasons for lower agreement were imprecise terms, insufficient knowledge on postnatal consequences, theoretical terms that are unlikely to occur in isolation, and the possibility of observing a range of severity that might be decisive for the classification of either a malformation or variation. The attendees concluded that "grey-zone" anomalies will never disappear completely and that for the assessment, the grade of severity and/or the frequency of the observation can be decisive for the terminology chosen. A Joint IPCS/IFTS Project was proposed to further consensus of terminology and classification and to link these anomalies to pictures at different skeletal sites. In order to support the harmonisation of regulatory decisions, it was proposed to establish a "Clearinghouse" System under the umbrella of the IPCS. The Clearinghouse could be contacted either by the regulatory authorities or by any company to clarify their queries, particularly with regard to registration or authorisation processes. Finally, it was recommended to also carry out a similar survey on "soft tissue anomalies" and "external findings." The results of this survey will be discussed at a Joint IPCS/IFTS Workshop in Berlin in 2002.

Abnormalities, Drug-Induced↗

PubMedDate not supplied

Expression of macrophage products after in vitro infection of human monocytes/macrophages with HIV.

We studied the response of monocytes/macrophages (MO/MAC) to lipopolysaccharide (LPS) and interferon-gamma (IFN gamma) stimulation with respect to the expression of macrophage-specific products, i.e. macrophage-colony-stimulating factor (M-CSF), c-fms, c-sis, tissue factors, transforming growth factor-beta (TGF beta) and interleukin-8 (IL8) after in vitro infection with HIV. The expression of IL8 was strongly elevated in HIV-infected cells, peaking at 4 h after stimulation with LPS. At that time, the uninfected control showed only weak expression of IL8. Other products, e.g. tissue factor, c-fms, M-CSF and TGF beta were not modulated after stimulation. In contrast to IL8, the expression of c-cis was significantly lower in infected cells after stimulation with IFN gamma compared to uninfected control cells.

Base Sequence↗