Untangling the effects of overexploration and overexploitation on organizational performance: The moderating role of environmental dynamism

Because a firm's optimal knowledge search behavior is determined by unique firm and industry conditions, organizational performance should be contingent oil the degree to which a firm's actual level of knowledge search deviates from the optimal level. It is thus hypothesized that deviation from the optimal search, in the form of either overexploitation or overexploration, is detrimental to organizational performance. Furthermore, the negative effect of search deviation oil organizational performance varies with environmental dynamism: that is, overexploitation is expected to become more harmful. whereas overexploration becomes less so with all increase in environmental dynamism. The empirical analyses yield results consistent with these arguments. Implications for research and practice are correspondingly discussed

Gel filtration of urine: a method to detect nephrotoxicity in rats

Sephadex G-100 gel filtration of urine from male Wistar rats revealed 3 protein peaks: peak I (eluted with the void volume of the column), peak II (Mr between 67 000 and 43 000), and peak III (Mr about 13 700). Nephrotoxic compounds were given as a single i.p. injection. Peak I, and especially peak II were significantly increased in 24-h urine samples from rats receiving mercuric acetate (1.58 mg/kg), mercuric trifluoroacetate (MTFA) (2.22 mg/kg), sodium ethylmercurithiosalicylate (EMTSA) (20.2 mg/kg), sodium tetrathionate (250 mg/kg), ammonium fluoride (18.5 mg/kg), paramomycin sulfate (800 mg/kg), ochratoxin A (5 mg/kg) and cis-platinum (4 mg/kg). It is concluded that gel filtration of urine can be used as a method to detect nephrotoxicity in rats</p

Interaction of the mycotoxin penicillic acid with glutathione and rat liver glutathione S-transferases

The in vitro interaction of the mycotoxin penicillic acid (PA) with rat liver glutathione S-transferase (GST) was studied using reduced glutathione and 1-chloro-2,4-dinitrobenzene as substrates. The inhibition of the GST activity by PA in crude extracts was dose dependent. Each of the different GST isoenzymes was inhibited, albeit at different degrees. Kinetic studies never revealed competitive inhibition kinetics. The conjugation of PA with GSH occurred spontaneously; it was not enzymatically catalyzed by GST, indicating that an epoxide intermediate is not involved in conjugation. The direct binding of PA to GST provides an additional detoxication mechanism</p

N-acetyl-(1-amino-2-naphthol-6-sulphonic acid), a common metabolite of sunset yellow FCF, orange GGN and 1-amino-2-naphthol-6-sulphonic acid in rat urine

Sunset Yellow FCF, Orange GGN and 1-amino-2-naphthol-6-sulphonic acid (ANSA) were administered to male Wistar rats by stomach intubation. Aromatic sulphonic acids excreted in 24-h urines after enzymatic cleavage of the azo link in the dyes were isolated using a thoroughly elaborated ion-pair extraction method and further separated by means of a reversed-phase ion-pair liquid chromatographic system. Blank 24-h rat urines were extracted and run at the same time under identical analytical circumstances. In addition to the peaks corresponding to sulphanilic and metanilic acid and their N-acetylated derivatives, which are metabolites arising from Sunset Yellow FCF and Orange GGN, respectively, an important common peak appeared on the chromatograms, which was absent from the blank urine extracts. After analysis of 24-h urine of rats that had received ANSA, a peak with the same retention time as this unknown common peak could be detected under the same liquid chromatographic conditions, the retention time of which was different from that of the ANSA standard. However, after derivatization of the ANSA standard with acetic anhydride, followed by liquid chromatographic examination of the derivatised mixture, two peaks appeared on the chromatogram, the first of which had the same retention time and the same UV-spectrum as the unknown common peak in rat urine extracts. By means of semi-preparative liquid chromatographic separation and isolation, followed by further purification over a cation-exchange resin, the compound corresponding to the unknown common peak could be identified by FT-PMR spectroscopy as N-acetyl-ANSA</p

Cystathionine pathway-dependent cytotoxicities of diethyl maleate and diamide in rat and human hepatoma-derived cell cultures

Glutathione (GSH) plays a role in many toxicologically important metabolic processes. It was previously established that L-buthionine S,R-sulphoximine (BSO), a specific inhibitor of (- glutamylcysteine synthetase, reduces the GSH content more efficiently in rat (Fa32) than in human (HEp-G2) hepatoma-derived cells. We therefore investigated whether the cystathionase inhibitor propargylglycine (PPG) could further decrease the BSO-induced GSH depletion in HEp-G2 cells. The influence of the cystathionine precursors N-acetylmethionine, methionine and homocysteine on the cytotoxicity of diethyl maleate (DEM) and diamide [1,1&#039;-azobis(N,N-dimethylformamide)] was also investigated. PPG reduced the GSH content in both cell lines. A further GSH decrease in HEp-G2 was obtained when using a BSO + PPG combination containing relatively high concentrations of PPG. BSO diminished the toxicity of PPG. Homocysteine was the most efficacious of the tested cystathionine precursors in increasing the GSH content and reducing the cytotoxicity of DEM and diamide in Fa32 and HEp-G2 cells</p