Synthesis of new 2-arylamino-6-trifluoromethylpyridine-3-carboxylic acid derivatives and investigation of their analgesic activity

A new series of 2-arylamino-6-trifluoromethyl-3-carboxylic acid derivatives was synthesized and assayed in vivo for their analgesic properties by means of writhing test in rats. When compared to aspirin, ibuprofen and flufenamic acid some of the new compounds exhibited a comparable or improved analgesic activity and a lower ulcerogenic effect.     

MASSUGU2 encodes Aux/IAA19, an auxin-regulated protein that functions together with the transcriptional activator NPH4/ARF7 to regulate differential growth responses of hypocotyl and formation of lateral roots in Arabidopsis thaliana

We have isolated a dominant, auxin-insensitive mutant of Arabidopsis thaliana, massugu2 (msg2), that displays neither hypocotyl gravitropism nor phototropism, fails to maintain an apical hook as an etiolated seedling, and is defective in lateral root formation. Yet other aspects of growth and development of msg2 plants are almost normal. These characteristics of msg2 are similar to those of another auxin-insensitive mutant, non-phototropic hypocotyl4 (nph4), which is a loss-of-function mutant of AUXIN RESPONSE FACTOR7 (ARF7) (Harper et al., 2000). Map-based cloning of the MSG2 locus reveals that all four mutant alleles result in amino acid substitutions in the conserved domain II of an Auxin/Indole-3-Acetic Acid protein, IAA19. Interestingly, auxin inducibility of MSG2/IAA19 gene expression is reduced by 65% in nph4/arf7. Moreover, MSG2/IAA19 protein binds to the C-terminal domain of NPH4/ARF7 in a Saccharomyces cerevisiae (yeast) two-hybrid assay and to the whole latter protein in vitro by pull-down assay. These results suggest that MSG2/IAA19 and NPH4/ARF7 may constitute a negative feedback loop to regulate differential growth responses of hypocotyls and lateral root formation.     

Salinity up-regulates the antioxidative system in root mitochondria and peroxisomes of the wild salt-tolerant tomato species Lycopersicon pennellii

The effect of salinity on the antioxidative system of root mitochondria and peroxisomes of a cultivated tomato Lycopersicon esculentum (Lem) and its wild salt-tolerant related species L. pennellii (Lpa) was studied. Salt stress induced oxidative stress in Lem mitochondria, as indicated by the increased levels of lipid peroxidation and H(2)O(2). These changes were associated with decreased activities of superoxide dismutase (SOD) and guaiacol peroxidases (POD) and contents of ascorbate (ASC) and glutathione (GSH). By contrast, in mitochondria of salt-treated Lpa plants both H(2)O(2) and lipid peroxidation levels decreased while the levels of ASC and GSH and activities of SOD, several isoforms of ascorbate peroxidase (APX), and POD increased. Similarly to mitochondria, peroxisomes isolated from roots of salt-treated Lpa plants exhibited also decreased levels of lipid peroxidation and H(2)O(2) and increased SOD, ascorbate peroxidase (APX), and catalase (CAT) activities. In spite of the fact that salt stress decreased activities of antioxidant enzymes in Lem peroxisome, oxidative stress was not evident in these organelles.     

A cohort study of thyroid cancer and other thyroid diseases after the Chornobyl accident: objectives, design and methods

The thyroid gland in children is one of the organs that is most sensitive to external exposure to X and gamma rays. However, data on the risk of thyroid cancer in children after exposure to radioactive iodines are sparse. The Chornobyl accident in Ukraine in 1986 led to the exposure of large populations to radioactive iodines, particularly (131)I. This paper describes an ongoing cohort study being conducted in Belarus and Ukraine that includes 25,161 subjects under the age of 18 years in 1986 who are being screened for thyroid diseases every 2 years. Individual thyroid doses are being estimated for all study subjects based on measurement of the radioactivity of the thyroid gland made in 1986 together with a radioecological model and interview data. Approximately 100 histologically confirmed thyroid cancers were detected as a consequence of the first round of screening. The data will enable fitting appropriate dose-response models, which are important in both radiation epidemiology and public health for prediction of risks from exposure to radioactive iodines from medical sources and any future nuclear accidents. Plans are to continue to follow-up the cohort for at least three screening cycles, which will lead to more precise estimates of risk.     

Asymmetric production of surface-dividing and non-surface-dividing cortical progenitor cells

Mature neocortical layers all derive from the cortical plate (CP), a transient zone in the dorsal telencephalon into which young neurons are continuously delivered. To understand cytogenetic and histogenetic events that trigger the emergence of the CP, we have used a slice culture technique. Most divisions at the ventricular surface generated paired cycling daughters (P/P divisions) and the majority of the P/P divisions were asymmetric in daughter cell behavior; they frequently sent one daughter cell to a non-surface (NS) position, the subventricular zone (SVZ), within a single cell-cycle length while keeping the other mitotic daughter for division at the surface. The NS-dividing cells were mostly Hu+ and their daughters were also Hu+, suggesting their commitment to the neuronal lineage and supply of early neurons at a position much closer to their destiny than from the ventricular surface. The release of a cycling daughter cell to SVZ was achieved by collapse of the ventricular process of the cell, followed by its NS division. Neurogenin2 (Ngn2) was immunohistochemically detected in a certain cycling population during G1 phase and was further restricted during G2-M phases to the SVZ-directed population. Its retroviral introduction converted surface divisions to NS divisions. The asymmetric P/P division may therefore contribute to efficient neuron/progenitor segregation required for CP initiation through cell cycle-dependent and lineage-restricted expression of Ngn2.     

Enthesopathies--proposal of a standardized scoring method and applications

Enthesopathies are alterations that could be present at entheses. Two types of enthesopathies have been defined: osteophytic (OF) and osteolytic (OL). In the present paper, we propose a standardized method to score the degree of development of each form of enthesopathy. With this method, the intra- and interobserver errors are less than 50%. The standard was used to study a sample (113 individuals) deriving from osteological collections from the late XIX-early XX century. Information about the age, sex and occupation of the individuals is available. This study demonstrated an effect of age on the form and the degree of development of enthesopathies. The influence of factors related to sex and occupation cannot be excluded. Therefore, functional interpretations of data on enthesopathies in osteoarchaeological series must take account of the estimated age and sex of the specimens and the distribution of the lesions within a single skeleton.     

Small cooperative activity of old rat hepatocytes may depend on composition of the intercellular medium

Ultradian oscillations of protein synthesis were used as a marker of hepatocyte synchronous cooperative activity producing a common rhythm in vitro; amplitude of the rhythm defines expression of the cell cooperation. Dense synchronous and sparse non-synchronous rat hepatocyte cultures on slides in a serum-free incubation medium 199 supplemented with 0.2 mg/ml albumin and 0.5 microg/ml insulin have been studied. The amplitude of the rhythm averaged approximately 2x in dense cultures of young (3 month old) rats than in old (2 year old) rats. But some cultures of young rats had the amplitude patterns similar to cultures of old rats, and vice versa. Addition to the medium of either 0.3 microM bovine brain gangliosides or 2 microM phenylephrine resulted in increase of the oscillation amplitude in dense cultures of old rats to the level inherent in young ones. Addition to the medium of 10% rat blood serum in non-synchronous sparse cultures from young rats resulted in detection of a protein synthetic rhythm. Although after serum from young rats, the rhythm expression was high, the rhythm after serum from old rats had been given was weak. Addition of gangliosides to old-rat serum resulted in synchronization of sparse cultures with amplitudes inherent of young-rat serum. The data tend to the conclusion that cell cooperation depends to a greater extent on the composition of the medium rather than on the age of the cell or animal.     

Effects of excess and deprivation of serotonin on in vitro neuronal differentiation

The neurotransmitter serotonin (5HT) possesses developmental functions in vertebrates and invertebrates. Rodent embryos express 5HT receptors even before neural development, but the role of this neurochemical seems to be particularly important during axonal morphogenesis and differentiation and in neural crest cell migration. Moreover, 5HT inhibitors are teratogenic in mammals, inducing brain and heart abnormalities. The aim of this study was to investigate the effects of nonphysiological concentrations of 5HT (5HT excess as well as deprivation) on developing rat neural cells using the micromass method. This simple and rapid micromass method allows the culture of mesencephalic cells capable of achieving and maintaining a significant degree of differentiation. Mesencephalic cells from 13 d post coitum (pc) rat were cultured and exposed to exogenous 5HT (1, 10, 50, or 100 microM) or to the specific 5HT2 receptor inhibitor mianserin (0.5, 5, 25, or 50 microM) during the whole culture period (5 d). The micromass morphology, the cytoskeletal organization, the pathological apoptosis, and the differentiative capability of cultured mesencephalic cells have been analyzed. The results show that 10-100 microM 5HT and 0.5-50 microM mianserin are able to disrupt the normal micromass morphology; 5HT and mianserin are unable to interfere with the cytoskeletal structures; mianserin (but not 5HT) induces pathological apoptosis on micromass cells at concentration levels of 0.5-50 microM; 5HT (but not mianserin) alters the neural differentiation at concentration levels of 10-100 microM. In conclusion, our results demonstrate that an excess of 5HT inhibits the capability of mesencephalic neurons to differentiate as shown by the alterations of the expression of the neuronal differentiative proteins glial-derived neurotrophic factor and Neu-N; on the other hand, the blocking of 5HT2 receptors induces apoptosis in differentiating neurons.