Radiation modulating properties of derivates of 1,4-dihydropyridine and 1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8 dione

First attempt to analyse radiation modifying action of 52 compounds--derivatives of 1,4-dihydropyridine is presented. Many of these compounds have electrodonating and antioxidative activities. Local radioprotective effects of the substances has been studied using experimental model with partial beta- and X-rays exposure of sole skin in rats to doses of 40 and 30 Gy. Comparison of drug effectiveness and chemical structure revealed the changes of activity dependence due to modification of peripheral radicals of 1,4-dihydropyridine ring. Radioprotective and radiosensitizing compounds with general low toxicity have been found. It is suggested to use the most active compounds for the development of medicinal forms for prevention of local skin and mucosal radiation injuries. Positive results have been obtained with dieton a radioprotective compound of the same type, in radiotherapy.     

An engineered PrPsc-like molecule from the chimera of mammalian prion protein and yeast Ure2p prion-inducing domain

Production of the pathogenic prion isoform PrP^sc-like molecules is thought to be useful forunderstanding the mysterious mechanism of conformational conversion process of prion diseases andproving the “protein-only“ hypothesis. In this report, an engineered PrP^sc-like conformation was producedfrom a chimera of mammalian bovine prion protein (bPrP) and yeast Ure2p prion-inducing domain (UPrD).Compared with the normal form of bPrP, the engineered recombinant protein, termed bPrP-UPrD,spontaneously aggregated into ordered fibrils under physiological condition, displaying amyloid-likecharacteristics, such as fibrillar morphology, birefringence upon binding to Congo red and increasedfluorescence intensity with Thioflavine T. Limited resistance to protease K digestion and CD spectroscopyexperiments suggested that the structure of bPrP-UPrD had been changed, and adopted a new, high contentB-sheet conformation during the fibrils formation. Moreover, bPrP-UPrD amyloid fibrils could recruit moresoluble forms into the aggregates. Therefore, the engineered molecules could mimic significant behaviors of PrP^se and will be helpful for further understanding the mechanism of conformational conversion process.     

Neither lipophilicity nor membrane-perturbing potency of phenothiazine maleates correlate with the ability to inhibit P-glycoprotein transport activity

Although phenothiazines are known as multidrug resistance modifiers, the molecular mechanism of their activity remains unclear. Since phenothiazine molecules are amphiphilic, the interactions with membrane lipids may be related, at least partially, to their biological effects. Using the set of phenothiazine maleates differing in the type of phenothiazine ring substitution at position 2 and/or in the length of the alkyl bridge-connecting ring system and side chain group, we investigated if their ability to modulate the multidrug resistance of cancer cells correlated with model membrane perturbing potency. The influence exerted on lipid bilayers was determined by liposome/buffer partition coefficient measurements (using the absorption spectra second-derivative method), fluorescence spectroscopy and calorimetry. Biological effects were assessed by a flow cytometric functional test based on differential accumulation of fluorescent probe DiOC(2)(3) by parental and drug-resistant cells. We found that all phenothiazine maleates were incorporated into lipid bilayers and altered their biophysical properties. With only few exceptions, the extent of membrane perturbation induced by phenothiazine maleates correlated with their lipophilicity. Within the group of studied derivatives, the compounds substituted with CF(3)- at position 2 of phenothiazine ring were the most active membrane perturbants. No clear relation was found between effects exerted by phenothiazine maleates on model membranes and their ability to modulate P-glycoprotein transport activity.     

Genetic Diversity of Ostreopsis ovata (Dinophyceae) from Malaysia

The genus Ostreopsis is an important component of benthic and epiphytic dinoflagellate assemblages in coral reefs and seaweed beds of Malaysia. Members of the species may produce toxins that contribute to ciguatera fish poisoning. In this study, two species have been isolated and cultured, Ostreopsis ovata and Ostreopsis lenticularis. Analyses of the 5.8S subunit and internal transcribed spacer regions ITS1 and ITS2 of the ribosomal RNA gene sequences of these two species showed that they are separate species, consistent with morphological designations. The nucleotide sequences of the 5.8S subunit and ITS1 and ITS2 regions of the rRNA gene were also used to evaluate the interpopulation and intrapopulation genetic diversity of O. ovata found in Malaysian waters. Results showed a low level of sequence divergence within populations. At the interpopulation level, the rRNA gene sequence distinguished two groups of genetically distinct strains, representative of a Malacca Straits group (isolates from Port Dickson) and a South China Sea group (isolates from Pulau Redang and Kota Kinabalu). Part of the sequences in the ITS regions may be useful in the design of oligonucleotide probes specific for each group. Results from this study show that the ITS regions can be used as genetic markers for taxonomic, biogeographic, and fine-scale population studies of this species. Received September 15, 2000; accepted December 15, 2000     

黑龙江省金色蝗属一新种 (直翅目：蝗总科)

 记述了采自松嫩草原的雏蝗属Chorthippus Fieber一新种, 即吉林雏蝗Chorthippus jilinensis sp. Nov.,并与其近似种翠饰雏蝗C.dichrous (Ev.)做了比较。模式标本保存于东北师范大学生命科学学院动物标本室。     

Purification and characterization of recombinant microsomal prostaglandin E synthase-1

Recombinant human microsomal prostaglandin E(2) synthase-1 (mPGES-1) was expressed in a baculovirus-Sf9 cell system. The mPGES-1 was solubilized from Sf9 cell membranes with diheptanoylphosphatidylcholine and purified in the presence of octylglucoside using hydroxyapatite column chromatography. The K(m) values of the substrates PGH(2) and GSH were 14 microM and 0.75 mM, respectively, with the purified enzyme. The specific activity (4 micromol/min/mg) was increased 3-5-fold by non-ionic and zwitterionic detergents. Kinetic analysis showed that dodecylmaltoside increases V(max) but does not affect the K(m) values of either substrate. Several other thiol-containing compounds were tested as glutathione replacements, none of which yielded detectable enzyme activity. During enzyme catalysis, glutathione was not oxidized and therefore can be considered an enzyme cofactor. No glutathione transferase or peroxidase activity could be determined with a range of potential substrates. The results show that purified mPGES-1 has a specific activity similar to Cox-2, consistent with its postulated role in Cox-2 mediated PGE(2) formation.     

Systematic review of comparative efficacy and tolerability of calcipotriol in treating chronic plaque psoriasis

ObjectivesTo evaluate the comparative efficacy and tolerability of topical calcipotriol in the treatment of mild to moderate chronic plaque psoriasis.DesignQuantitative systematic review of randomised controlled trials.Subjects6038 patients with plaque psoriasis reported in 37 trials.ResultsCalcipotriol was at least as effective as potent topical corticosteroids, calcitriol, short contact dithranol, tacalcitol, coal tar, and combined coal tar 5%, allantoin 2%, and hydrocortisone 0.5%. Calcipotriol caused significantly more skin irritation than potent topical corticosteroids (number needed to treat to harm for irritation 10, 95% confidence interval 6 to 34). Calcipotriol monotherapy also caused more irritation than calcipotriol combined with a potent topical corticosteroid (6, 4 to 8). However, the number needed to treat for dithranol to produce lesional or perilesional irritation was 4 (3 to 5). On average, treating 23 patients with short contact dithranol led to one more patient dropping out of treatment owing to adverse effects than if they were treated with calcipotriol.ConclusionsCalcipotriol is an effective treatment for mild to moderate chronic plaque psoriasis, more so than calcitriol, tacalcitol, coal tar, and short contact dithranol. Only potent topical corticosteroids seem to have comparable efficacy at eight weeks. Although calcipotriol caused more skin irritation than topical corticosteroids this has to be balanced against the potential long term effects of corticosteroids. Skin irritation rarely led to withdrawal of calcipotriol treatment. Longer term comparative trials of calcipotriol versus dithranol and topical corticosteroids are needed to see whether these short term benefits are mirrored by long term outcomes such as duration of remission and improvement in quality of life.     

Susceptibility to selected coagulase-negative chemotherapeutic agents of methicillin resistant staphylococci isolated from clinical materials in 1997-1998

The study was aimed at assessment of the sensitivity of methicillin-resistant coagulase-negative staphylococci isolated from clinical material in 1997/1998 to selected chemotherapeutic agents. The investigated material comprised 96 methicillin-resistant coagulase-negative staphylococci from hospital and ambulatory infections isolated during the period from April 1997 to May 1998. Species affiliation was determined by classical identification methods and commercial diagnostic tests for identification of staphylococci. Methicillin resistance was determined by agar disk-diffusion method and screening. Sensitivity to chemotherapeutics was determined by agar disk-diffusion method and agar dilution methods. All the investigated strains were sensitive to nitrofurantoin, furazolidone and vancomycin. To teicoplanin--the second glycopeptide antibiotic--84% strains were sensitive, whereas the percentages of resistant and moderately sensitive strains amounted to 5.2% and 10.4%, respectively. 85% and 82% of coagulase-negative staphylococcal strains were sensitive to fusidic acid and mupirocin. Considerable differences were noted with respect to sensitivity to aminoglycoside group antibiotics. About 35% of strains were sensitive to gentamicin, and 90% sensitive to netilmicin. Ca. 40% of coagulase-negative staphylococci were resistant both to cotrimoxazole and trimethoprim, which, in view of 98% resistance to the second component of cotrimoxazole, may be associated with the activity of only one of the components of the drug--trimethoprim.     

Identifying novel regulators of shoot meristem development

New organs are initiated throughout the life span of higher plants. This process occurs at the shoot meristem, which is initiated during embryogenesis and is later responsible for generating the above-ground portion of the plant. The shoot meristem can be thought of as having two zones, a central zone containing meristematic cells in an undifferentiated state, and a surrounding peripheral zone where cells enter a specific developmental pathway toward a differentiated state. Recent advances have revealed several genes that specifically regulate meristem development inArabidopsis. However, extensive mutagenesis by several labs have identified only a handful, of loci that appear to specifically regulate shoot meristem development. We have undertaken an enhancer/suppressor mutagenesis of an existing meristem mutant (clv1) and have identified novel regulators of meristem development. The extended abstract of a paper presented at the 13th International Symposium in Conjugation with Award of the International Prize for Biology “Frontier of Plant Biology”