Pharmacokinetic studies on aztreonam in late pregnancy in sheep and humans

The transplacental passage of single intravenous doses of aztreonam (AZT), 1 g or 2 g, was examined in 7 sheep and 14 women in late pregnancy, respectively and the obtained data were analyzed by a two-compartment model. The obtained results were summarized as follows. After single 2 g intravenous doses were given to pregnant sheep, the mean peak level of AZT in maternal blood was 83.79 micrograms/ml and the half-life of the beta-phase was 1.525 hours. After single 1 g intravenous doses were administered to pregnant women, the mean peak level of AZT in blood was 102.62 micrograms/ml and the half-life of beta-phase was 2.128 hours. The peak levels in umbilical venous blood and amniotic fluid were 14.43 micrograms/ml and 11.86 micrograms/ml, respectively.     

Up-regulation of histamine H1 receptors in an allergic rat nasal mucosa model

Inflammation Research -     

Effect of aging on NADPH-diaphorase neurons in laterodorsal tegmental nucleus and striatum of mice

Age-related changes of reduced nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d)-containing neurons were examined quantitatively in the laterodorsal tegmental nucleus (TLD) and the caudate-putamen of mice. Six 2-month-old and six 25- to 30-month-old DDD mice were studied using computer-assisted image analysis. Although no age-related changes in neuronal counts were found in the TLD, the cell size in this nucleus showed a statistically significant reduction with aging. In addition, the degree of the age-related neuronal shrinkage differed within the TLD; the most significant occurring in the rostral, less in the caudal third and no significant alteration being found in the middle third portion of TLD. In contrast, NADPH-d-positive neurons in the striatum did not show distinct age-related changes. NADPH-d-containing neurons in the TLD correspond to cholinergic cells, which project to the forebrain. Thus, the age-related shrinkage of NADPH-d neurons in the TLD may be related to the cholinergic dysfunctions seen in the forebrain of senescent mice.     

Purification and partial characterization of heat-stable enterotoxin of enterotoxigenic Escherichia coli.

Heat-stable enterotoxin was purified from a strain of enterotoxigenic Escherichia coli 53402 A-1 from human intestine. The cells were cultured in Casamino Acids-yeast extract-salts medium, and the purification procedure consisted of protamine sulfate treatment of the culture supernatant, ultrafiltration with an Amicon PM-10 membrane, diethylaminoethyl-cellulose column chromatography, hydroxyapatite column chromatography, Bio-Gel P-10 gel filtration, 90% ethanol extraction, and preparative polyacrylamide gel disc electrophoresis. About 300-fold purification was achieved, with a yield of about 12%. However, the homogeneity of the purified heat-stable enterotoxin was not rigorously demonstrated. The purified heat-stable enterotoxin had an absorption maximum at about 275 nm, and its isoelectric point was about 3.90. The molecular weight of the purified heat-stable enterotoxin was ca. 4,000 by Sephadex G-100 gel filtration. The minimum effective dose of purified heat-stable enterotoxin was about 2.5 ng in the suckling mouse assay. The purified heat-stable enterotoxin gave a positive reaction in not only the suckling mouse assay but also the mouse intestinal loop test and the guinea pig skin permeability test.     

Bcl11b is required for differentiation and survival of alphabeta T lymphocytes

The gene Bcl11b, which encodes zinc finger proteins, and its paralog, Bcl11a, are associated with immune-system malignancies. We have generated Bcl11b-deficient mice that show a block at the CD4-CD8- double-negative stage of thymocyte development without any impairment in cells of B- or gammadelta T cell lineages. The Bcl11b-/- thymocytes showed unsuccessful recombination of V(beta) to D(beta) and lacked the pre-T cell receptor (TCR) complex on the cell surface, owing to the absence of Tcrb mRNA expression. In addition, we saw profound apoptosis in the thymus of neonatal Bcl11b-/- mice. These results suggest that Bcl11b is a key regulator of both differentiation and survival during thymocyte development.     

Changes in fibre-type composition and myosin heavy-chain IId isoform in rat soleus muscle during recovery period after hindlimb suspension

We examined the changes in myosin heavy-chain (HC) isoforms and fibre-type composition in rat soleus muscle using both myosin adenosine triphosphatase staining and sodium dodecyl sulphate/polyacrylamide gel electrophoresis (SDS-PAGE) analyses during the recovery period after 4 weeks of hindlimb suspension. Although there was no change in type IIc fibres after the suspension, an increase in this type of fibres was observed during the 1- to 4-week recovery period. The increase in type Ilc fibres was considered to be due to a shift from type Ila to IIc fibres. The SDS-PAGE analysis revealed the presence of the HC IId isoform, which was not observed in the control muscle, after a 4-week hindlimb suspension. The HC IId isoform gradually decreased over 3 weeks of recovery and disappeared in the 4th week of recovery after the suspension. These results suggest that the hypogravity conditions induced by hindlimb suspension stimulated the synthesis of the HC IId isoform, whereas an increase in mechanical load to the muscle accelerated the degradation of the HC IId isoform and the synthesis of type Ilc fibres during the recovery period after hindlimb suspension.     

MEG Characterization of Spontaneous Alpha Rhythm in the Human Brain

The present piece of research studied the spontaneous alpha rhythm of the human brain by combining the use of a whole-cortex neuromagnetometer and Magnetic Resonance Imaging. Single trials of spontaneous brain activity were recorded from ten human subjects asked to rest, with their eyes either closed or open, in relaxed wakefulness. MEG measurements were conducted over a period of one and a half years. The replicability of the results was confirmed for eight subjects out of ten. For three subjects, the alpha rhythm did not show any reductions due to the opening of the eyes. Both field map pattern and location of the estimated source were persistently stationary during each of the bursts of oscillations of the alpha rhythm. Dipoles were concentrated in clusters, indicating the existence of several spatially distributed sources. The calcarine fissure, the parieto-occipital sulcus and the surrounding occipital and parieto-occipital areas were identified as cortical sites of the brain where the alpha rhythm may originate. For four subjects, the majority of the sources were located near or in the calcarine fissure, while for five subjects, they were located near or in the parieto-occipital sulcus and for the remaining subject they were equally divided between the two generation sites.     

Cloning and nucleotide sequencing of Vero toxin 2 variant genes from Escherichia coli O91:H21 isolated from a patient with the hemolytic uremic syndrome

Cellular DNA extracted from Escherichia coli strain B2F1 (O91:H21) was found to contain two separate DNA sequences that hybridized with a Vero toxin 2 (VT2)-specific gene probe under stringent conditions. These two sequences were cloned and both were shown to encode a variant of Vero toxin 2 (VT2vh). The nucleotide sequences of the operons encoding VT2vh, designated as vtx2ha and vtx2hb, were determined. The two operons were nearly identical (99% overall DNA homology) and both encoded A subunits of 319 amino acid residues and B subunits of 89 amino acid residues, the A and B subunit genes being separated by a stretch of 14 bp. The A and B subunit genes of the vtx2ha operon exhibited 98.6% and 95.5% DNA homology, respectively, with those of the slt-II operon encoding Shiga-like toxin II (or VT2) cloned from a strain from a patient with hemorrhagic colitis, while the A and B subunit genes of the vtx2ha operon showed 94.5% and 82.8% DNA homology, respectively, with those of the slt-IIv operon encoding a SLT-II variant cloned from a strain isolated from a pig with edema disease. The nucleotide sequences of the presumed promoters and presumptive ribosome binding sites in the vtx2ha, vtx2hb, and slt-II, and slt-IIv operons were identical. These results indicate that nucleotide sequences encoding a family of VT2-related toxins are present in various strains of E. coli and that the sequences of the genes for A subunits are better conserved than those of the B subunit genes.