The inhibitory activity of natural products on plant p-hydroxyphenylpyruvate dioxygenase

The inhibitory activity of 34 natural products of various structural classes on hydroxyphenylpyruvate dioxygenase (HPPD), the target site for triketone herbicides, and the mode of interaction of selected natural products were investigated. Recombinant HPPD from arabidopsis is sensitive to several classes of natural compounds including, in decreasing order of sensitivity, triketones, benzoquinones, naphthoquinones and anthraquinones. The triketone natural products acted as competitive tight-binding inhibitors, whereas the benzoquinones and naphthoquinones did not appear to bind tightly to HPPD. While these natural products may not have optimal structural features required for in vivo herbicidal activity, the differences in their kinetic behavior suggest that novel classes of HPPD inhibitors may be developed based on their structural backbones.     

Response surface methodology for the optimization of ubiquinone self-nanoemulsified drug delivery system

The aim of the present study was to prepare and evaluate an optimized, self-nanoemulsified drug delivery system of ubiquinone. A 3-factor, 3-level Box-Behnken design was used for the optimization procedure with the amounts of Polyoxyl 35 castor oil (X₁), medium-chain mono- and diglyceride (X₂), and lemon oil (X₃) as the independent variables. The response variable was the cumulative percentage of ubiquinone emulsified in 10 minutes. Different ubiquinone release rates were obtained. The amount released ranged from 11% to 102.3%. Turbidity profile revealed 3 regions that were used to describe the progress of emulsion formation: lag phase, pseudolinear phase, and plateau turbidity. An increase in the amount of surfactant decreased turbidity values and caused a delay in lag time. Addition of cosurfactant enhanced the release rates. Increasing the amount of the eutectic agent was necessary to overcome drug precipitation especially at higher loading of surfactants and cosurfactants. Mathematical equations and response surface plots were used to relate the dependent and independent variables. The regression equation generated for the cumulative percentage emulsified in 10 minutes was Y1=90.9–22.1X₁+5.03X₂+13.95X₃+12.13X₁X₂+15.13X₁X₃-14.40X₁ ²-6.25X₃ ². The optimization model predicted a 93.4% release with X₁, X₂, and X₃ levels of 35, 35, and 30 respectively. The observed responses were in close agreement with the predicted values of the optimized formulation. This demonstrated the reliability of the optimization procedure in predicting the dissolution behavior of a self-emulsified drug delivery system. Published: February 8, 2002.     

Tetracycline-Cu(II) photo-induced fragmentation of serum albumin

The protein-damaging potential of photosensitized tetracycline hydrochloride alone and in combination with the metal ion Cu(II) was assessed using serum albumin as a model protein. Exposure of tetracycline to white light in an aqueous solution triggered the generation of significant amounts of reactive oxygen species (ROS) and engendered substantial protein damage. The appearance of distinct low-molecular-mass protein bands on 10% SDS-polyacrylamide gel ascertained the tetracycline concentration-dependent fragmentation of albumin. Photoexcited tetracycline in combination with 100 microM Cu(II) enhanced the protein fragmentation process with concurrent increase in free radical production. The significant release of acid-soluble amino groups and carbonyl groups from treated albumin provided quantitative estimation of protein fragmentation at 0-1.0 mM concentrations of tetracycline. Cu(II) ions per se did not cause any perceptible protein damage. The results with free radical quenchers suggested the role of hydroxyl radicals (*OH) in tetracycline-Cu(II)-induced protein fragmentation, as no superoxide dismutase (SOD)-mediated quenching effect was noted. The generation of free radicals upon tetracycline photoexcitation and consequent protein fragmentation may be considered as important factors in augmentation of tetracycline-induced phototoxic responses.     

Characterization of the estrogenic response to genistein in Japanese medaka (Oryzias latipes)

This study was designed to determine the estrogenic effect of the phytoestrogen genistein on several measures of endocrine function in adult Japanese medaka (Oryzias latipes) relative to 17-beta-estradiol. Adult animals of both sexes were exposed to 75, 750 and 30,000 ng/fish (average fish weight equals 0.26 g) of genistein by i.p. injection, with a positive control group treated with 300 ng/fish of 17-beta-estradiol, while a negative control group received a vehicle-only (corn oil) injection. Content of vitellogenin, the yolk glycoprotein made in the liver in response to estradiol stimulation, was measured using Western blots. Circulating estradiol and testosterone levels were measured using a steroid-enzyme immunosorbant assay. The ability of ovaries and testes to synthesize and release estradiol and testosterone was determined by ex vivo incubation of gonads with 25-hydroxycholesterol. Vitellogenin, while induced by 17-beta-estradiol, was not increased in the liver of individuals treated with genistein. In females, genistein treatment at 750 and 30,000 ng increased the estradiol production of ovaries more than the 17-beta-estradiol treatment. In males, genistein treatment resulted in decreased testosterone production from ex vivo testis and a comparable reduction in circulating testosterone level. The changes in vitellogenin, circulating steroids and ex vivo steroidogenesis in medaka in response to genistein are similar to that of 17-beta-estradiol. However, some endpoints are more sensitive to estradiol treatment (vitellogenin), while others are more sensitive to genistein (male testosterone and ovarian estrogenesis).     

Developing a laboratory animal model for perinatal endocrine disruption: the hamster chronicles

At the biomedical, regulatory, and public level, considerable concern surrounds the concept that inappropriate exposure to endocrine-disrupting chemicals, especially during the prenatal and/or neonatal period, may disrupt normal reproductive tract development and adult function. The intent of this review was to 1. Describe some unique advantages of the hamster for perinatal endocrine disruptor (ED) studies, 2. Summarize the morphological and molecular consequences of exposure to the established perinatal ED, diethylstilbestrol, in the female and male hamster, 3. Present some new, histomorphological insight into the process of neonatal diethylstilbestrol-induced disruption in the hamster uterus, and 4. Introduce recent efforts and future plans to evaluate the potency and mechanism of action of other putative EDs in the hamster experimental system. Taken together, the findings indicate that the hamster represents a unique and sensitive in vivo system to probe the phenomenon of endocrine disruption. The spectrum of candidate endpoints includes developmental toxicity, neoplasia, and more subtle endpoints of reproductive dysfunction.     

The effect of hyperthermia on the induction of cell death in brain, testis, and thymus of the adult and developing rat

Stressful stimuli can elicit 2 distinct reactive cellular responses, the heat shock (stress) response and the activation of cell death pathways. Most studies on the effects of hyperthermia on the mammalian nervous system have focused on the heat shock response, characterized by the transient induction of Hsps, which play roles in repair and protective mechanisms. This study examines the effect of hyperthermia on the induction of cell death via apoptosis, assayed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling and active caspase 3 cytochemistry, in the adult rat brain, testis, and thymus. Results show that a fever-like increase in temperature triggered apoptosis in dividing cell populations of testis and thymus, but not in mature, postmitotic cells of the adult cerebellum. These differential apoptotic responses did not correlate with whole-tissue levels of Hsp70 induction. We further investigated whether dividing neural cells were more sensitive to heat-induced apoptosis by examining the external granule cell layer of the cerebellum at postnatal day 7 and the neuroepithelial layers of the neocortex and tectum at embryonic day 17. These proliferative neural regions were highly susceptible to hyperthermia-induced apoptosis, suggesting that actively dividing cell populations are more prone to cell death induced by hyperthermia than fully differentiated postmitotic neural cells.     

小麦和无融合生殖披碱草杂交后代(BC2F2)的无融合生殖及胚胎发育过程中的异常现象研究

对小麦（Triticum aestivum）和无融合生殖披碱草（Elymus rectisetus）的染色体数目为42的杂种后代（BC2F2）单株进行了RAPD检测和胚胎学研究,RAPD检测结果表明：染色体数目为42条的BC2F2单株的遗传组成与普通小麦的遗传组成十分接近,但是在部分单株中出现了披碱草的特异带。由此可以推测,经过回交和自交后小麦草的部分染色体片段已经整合进了小麦的染色体。在部分BC2F2单株胚胎学切片中发现了较高比例的（5%左右）双孢原、早发胚以及多胚囊等无融合生殖现象,直接表明了无融合生殖基因转移。由于基因整合的多样性。无融合生殖基因在有些单株中并没有充分表达,从而造成了某些单株胚胎发育的异常。     

Solvent effects on the stability of nifuroxazide complexes with cobalt(II), nickel(II) and copper(II) in alcohols

A spectrophotometric study of the complexation of nifuroxazide with cobalt(II), nickel(II) and copper(II) was carried out in different alcohols. The formation of a complex in each case is reported and their stability constants have been calculated. For a given solvent, the stability of the complexes increases from cobalt to copper. In the case of copper(II), the stability varies as an inverse function of the dielectric constant of the solvent. A possible structure of the complex is proposed.