Effects of probenecid and cimetidine on renal disposition of ofloxacin in rats

The renal handling of ofloxacin in rats which were given ofloxacin either alone or in combination with probenecid or cimetidine was studied. In the presence of cimetidine or probenecid, ofloxacin's total and renal clearances were reduced and its half-life was prolonged. This suggests that ofloxacin is secreted by both the anionic and cationic transport systems.     

Pretreatment with a 55-kDa tumor necrosis factor receptor-immunoglobulin fusion protein attenuates activation of coagulation, but not of fibrinolysis, during lethal bacteremia in baboons

Baboons (Papio anubis) receiving a lethal intravenous infusion with live Escherichia coli were pretreated with either a 55-kDa tumor necrosis factor (TNF) receptor-IgG fusion protein (TNFR55:IgG) (n = 4, 4.6 mg/kg) or placebo (n = 4). Neutralization of TNF activity in TNFR55:IgG-treated animals was associated with a complete prevention of mortality and a strong attenuation of coagulation activation as reflected by the plasma concentrations of thrombin-antithrombin III complexes (P < .05). Activation of fibrinolysis was not influenced by TNFR55:IgG (plasma tissue-type plasminogen activator and plasmin-alpha2-antiplasmin complexes), whereas TNFR55:IgG did inhibit the release of plasminogen activator inhibitor type I (P < .05). Furthermore, TNFR55:IgG inhibited neutrophil degranulation (plasma levels of elastase-alpha1-antitrypsin complexes, P < .05) and modestly reduced release of secretory phospholipase A2. These data suggest that endogenous TNF contributes to activation of coagulation, but not to stimulation of fibrinolysis, during severe bacteremia.     

ESEM observation of thermal shock cracking

We report a simple method for a quick and efficient localization of thermal shock cracks as narrow as 1 micron or less, using Environmental Scanning Electron Microscopy (ESEM). The non-destructive character of the technique is exploited in order to observe relevant fractographic features of the crack pattern.     

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Forty Aspergillus japonicus and A. aculeatus strains, most of them wild-type isolates, were examined using various molecular and phenotypic techniques. The rDNAs proved to be invariable (even strains of the species A. aculeatus exhibited the same restriction profile), while the strains could be classified into seven different mtDNA RFLP groups. Hybridisation data suggest that six of these mtDNA types have certain common restriction sites, while mtDNA type 7, which was exhibited by some A. aculeatus strains, probably has quite different mtDNA organisation and their size was smallest among the strains studied. The RAPD technique and isoenzyme analysis revealed some variabilities within these RFLP groups and strain specific features could also be recognised. Carbon source assimilation spectra were found to be very distinctive for strains of A. japonicus, A. aculeatus and A. niger, providing a useful tool for pre-characterising new wild-type isolates of black Aspergilli. Only a limited correlation was observed between the dendrograms based on genotypic and phenotypic characters.     

Testosterone induces Ca2+ influx via non-genomic surface receptors in activated T cells

MalK is the ATP-hydrolyzing subunit of the binding protein-dependent ATP-binding-cassette (ABC) transport system for maltose from Salmonella typhimurium. In a recent hypothesis, Glu64 and Glu94 of MalK were proposed as candidates for 'catalytic carboxylate', common to ATP- and GTP-hydrolyzing proteins [Yoshida and Amano (1995) FEBS Lett. 359, 1-5]. Substitution of both residues and, additionally, Glu74 by either glutamine or glycine and valine, respectively, had no deleterious effect on maltose transport. Thus, our data disprove the above notion.     

Cell wall composition of vascular and parenchyma tissues in broccoli stems

Broccoli stems can become tough and stringy owing to excessive development of the vascular ring. Thickened cell walls from the vascular ring were isolated and their composition was determined. They were derived principally from anatomically recognisable xylem vessels, fibres and tracheids but contained an assemblage of polysaccharides typical of primary cell walls. Their pectin content was particularly high and they contained only 6% lignin as estimated by solid state ¹³C NMR spectroscopy. They did not differ markedly in composition from parenchyma cell walls within the same stems. Thus, despite their thickness and anatomical appearance, these cell walls resembled the walls of non‐woody cells in their polymer composition. Copyright © 2003 Society of Chemical Industry     

The mouse intraovarian insulin-like growth factor I system: departures from the rat paradigm

Although the rat intraovarian insulin-like growth factor I (IGF-I) system is well documented, the increasing availability of null mouse mutants for components of the IGF system necessitates characterization of the mouse model as well. Therefore, we undertook to define the components of the mouse intraovarian IGF-I system and to examine its operational characteristics. The cellular pattern of ovarian gene expression was comparable in the immature rat and mouse for IGF-I and the type I IGF receptor. In both species, IGF-I messenger RNA (mRNA) is selectively expressed by granulosa cells in growing, healthy appearing follicles. Type I IGF receptor mRNA was also concentrated in granulosa cells, but was uniformly expressed in all follicles large and small, healthy and atretic appearing alike. Cellular patterns of IGF-binding protein (IGFBP) gene expression were similar in mouse and rat, except in the case of IGFBP-2. IGFBP-2 mRNA was localized to the mouse granulosa cell, in contrast to its concentration in the rat thecal-interstitial compartment. This difference in IGFBP expression pattern was also noted in cultured mouse and rat granulosa cells. Although immunoreactive IGFBP-4 (24 and 28 kDa) and IGFBP-5 (29 kDa) were shared by both species, the cultured mouse granulosa cell also featured immunoreactive IGFBP-2 (30 kDa). The mouse paradigm further differed from its rat counterpart in that a maximal dose of FSH, previously shown to suppress the elaboration of rat granulosa cell-derived IGFBPs, was without effect. The addition of IGF-I proved stimulatory to the accumulation of the 28- to 29-kDa IGFBPs, as previously reported for the rat. However, IGF-I proved inhibitory to the accumulation of the 24-kDa IGFBP (presumptive nonglycosylated IGFBP-4); no consistent effect was reported for the rat model. Functional comparisons of mouse and rat ovarian cell cultures revealed qualitatively comparable FSH-stimulated steroidogenesis, disposition of radiolabeled pregnenolone, IGF-I-amplified FSH action, and IGFBP-mediated antigonadotropic activity. These findings indicate that the mouse intrafollicular IGF-I system differs from the rat paradigm in both the makeup and regulation of granulosa cell-derived IGFBPs as well as in the intensity and character of the steroidogenic process. Studies employing the mouse model must take into account these important distinctions relative to the more established rat paradigm.     

Nitrofurantoin-induced hepatotoxicity mediated by CD8+ T cells

Nitrofurantoin is a synthetic nitrofuran commonly used for the treatment and prophylaxis of urinary tract infections. We describe the case of a 75-yr-old woman who was taking nitrofurantoin as prophylaxis against recurrent urinary tract infections, and who subsequently developed pulmonary and hepatic toxicity. We postulate that a breakdown product of the drug or the drug itself complexed to an endogenous peptide is presented by the class I HLA antigen on the hepatocyte cell membrane, inducing cytotoxic T cell activation and subsequently, hepatocyte death.     

A VSG expression site-associated gene confers resistance to human serum in Trypanosoma rhodesiense

Twenty three isolates of Beauveria bassiana and 13 isolates of Metarhizium anisopliae were tested on third instar nymphs of Triatoma infestans, a serious vector of Chagas disease. Pathogenicity tests at saturated humidity showed that this insect is very susceptible to fungal infection. At lower relative humidity (50%), conditions expected in the vector microhabitat, virulence was significantly different among isolates. Cumulative mortality 15 days after treatment varied from 17.5 to 97.5%, and estimates of 50% survival time varied from 6 to 11 days. Maintaining lower relative humidity, four B. bassiana and two M. anisopliae isolates were selected for analysis of virulence at different conidial concentrations and temperatures. Lethal concentrations sufficient to kill 50% of insects (LC50) varied from 7.1 x 10(5) to 4.3 x 10(6) conidia/ml, for a B. bassiana isolate (CG 14) and a M. anisopliae isolate (CG 491) respectively. Most isolates, particularly B. bassiana isolates CG 24 and CG 306, proved to be more virulent at 25 and 30 degrees C, compared to 15 and 20 degrees C. The differential virulence at 50% humidity observed among some B. bassiana isolates was not correlated to phenetic groups in cluster analysis of RAPD markers. In fact, the B. bassiana isolates analyzed presented a high homogeneity (> 73% similarity).