Genotoxic activity of 1,2,3‐triazolyl modified furocoumarins and 2,3‐dihydrofurocoumarins

The furocoumarin backbone is a promising platform for chemical modifications aimed at creating new pharmaceutical agents. However, the high level of biological activity of furocoumarins is associated with a number of negative effects. For example, some of the naturally occurring ones and their derivatives can show genotoxic and mutagenic properties as a result of their forming crosslinks with DNA molecules. Therefore, a particularly important area for the chemical modification of natural furocoumarins is to reduce the negative aspects of their bioactivity. By studying a group of 21 compounds—1,2,3‐triazolyl modified derivatives of furocoumarin and peucedanin—using the SOS chromotest, the Ames test, and DNA‐comet assays, we revealed modifications that can neutralize the structure's genotoxic properties. Theoretical aspects of the interaction of the compound library were studied using molecular modeling and this identified the leading role of the polyaromatic molecular core that takes part in stacking‐interactions with the pi‐systems of the nitrogenous bases of DNA.     

Parameterization of the stomatal component of the DO3SE model for Mediterranean evergreen broadleaf species

An ozone (O3) deposition model (DO3SE) is currently used in Europe to define the areas where O3 concentrations lead to absorbed O3 doses that exceed the flux-based critical levels above which phytotoxic effects would be likely recorded. This mapping exercise relies mostly on the accurate estimation of O3 flux through plant stomata. However, the present parameterization of the modulation of stomatal conductance (g(s)) behavior by different environmental variables needs further adjustment if O3 phytotoxicity is to be assessed accurately at regional or continental scales. A new parameterization of the model is proposed for Holm oak (Quercus ilex), a tree species that has been selected as a surrogate for all Mediterranean evergreen broadleaf species. This parameterization was based on a literature review, and was calibrated and validated using experimentally measured data of g(s) and several atmospheric and soil parameters recorded at three sites of the Iberian Peninsula experiencing long summer drought, and very cold and dry winter air (El Pardo and Miraflores) or milder conditions (Tietar). A fairly good agreement was found between modeled and measured data (R2 = 0.64) at Tietar. However, a reasonable performance (R2 = 0.47-0.62) of the model was only achieved at the most continental sites when g(s) and soil moisture deficit relationships were considered. The influence of root depth on g(s) estimation is discussed and recommendations are made to build up separate parameterizations for continental and marine-influenced Holm oak sites in the future.     

Nutritional Requirements of <Emphasis Type="Italic">Lactobacillus delbrueckii</Emphasis> subsp. <Emphasis Type="Italic">lactis</Emphasis> in a Chemically Defined Medium

This study was undertaken to determine the nutritional requirements of Lactobacillus delbrueckii subsp. lactis and to develop a minimal chemically defined medium that supports sustained growth of these microorganisms. The single-omission technique was applied to each component of complete chemically defined medium in order to determine the nutritional requirements. L. delbrueckii subsp. lactis was prototrophic for alanine, glycine, aspartic acid, asparagine, glutamine, threonine, and proline. The lysine requirement was strain-dependent. Magnesium was the only essential oligoelement. These microorganisms also required uracil and guanine and adenine as pyrimidine and purine sources, respectively. In view of the nutritional requirements we designed a new minimal defined medium which supports sustained growth of L. delbrueckii subsp. lactis. This medium is simple and well defined, and should be preferable to complex media for conducting future biochemical, physiological, and genetic studies on L. delbrueckii subsp. lactis.     

Molecular phylogeny of two lineages of Leuciscinae cyprinids (Telestes and Scardinius) from the peri-Mediterranean area based on cytochrome b data

We examined phylogenetic relationships in two lineages of Leuciscinae cyprinid fishes based on the sequence data of the complete mitochondrial DNA region coding for the cytochrome b gene (1140 bp). Telestes includes obligate riverine, moderately cold water-adapted species whereas Scardinius comprises warm-adapted species living in lowland lakes and still waters of rivers and streams. We also analysed selected representatives of Leuciscus and Phoxinellus because the taxonomic status of some species belonging to these genera is dubious and they could be placed in the genus Telestes. The study includes 18 species, 43 populations, and 111 individuals from 9 of the 14 peri-Mediterranean ichthyogeographic districts. Clades recovered from the phylogenetic analyses do not support previous taxonomic assumptions based on morphology. Telestes, Leuciscus, and Phoxinellus do not form monophyletic assemblages; phylogenetic analyses suggest that L. polylepis, L. turskyi, P. croaticus, and P. metohiensis should be included in Telestes. Similarly, populations of Scardinius erythrophthalmus do not cluster together and the endangered S. scardafa, endemic to central Italy and surviving in a single locality, is nested within them. The radiations of Telestes and Scardinius occurred in different time periods. A major diversification of Telestes is consistent with a sea dispersal during the freshwater Messinian "Lago Mare" phase of the Mediterranean Sea. Cladogenetic events within Scardinius are likely related to the extension and confluence of river drainages in lowlands following multiple lowering of the sea level during the Quaternary glaciations.     

Social phobia

Social anxiety disorder (social phobia) is an irrational fear of being observed and judged by other people in various social settings. The individual is afraid that he or she will act in a way that will be humiliating or embarrassing. It is often a chronic, disabling condition that is characterized by a phobic avoidance of most social situations. Social anxiety disorder is the most frequent anxiety disorder (10-15%) that occurs in two subtypes--generalized and specific. It is a disorder that occurs during the adolescence and reflects negatively to the quality of life of an individual. Neurobiological basis of this disorder has not been explored yet. The disorder is frequently burdened with comorbidity with other anxiety disorders, depression and substance-related disorders. Only cognitive-behavioral techniques are desirable in the psychotherapeutic treatment of the disorder and the best results are achieved in combination with pharmacotherapy. The medicaments of choice in the treatment of social anxiety disorder are selective serotonin reuptake inhibitors. Anxiolytics should be used only as a supplementary in the acute phase. Treatment of social anxiety disorder should last at least 3 months up to one year.     

Beta 2-microglobulin-free HLA class I heavy chain epitope mimicry by monoclonal antibody HC-10-specific peptide

mAb HC-10 loses its reactivity with HLA class I (HLA-I) H chain (HC) following its association with beta(2)-microglobulin (beta(2)m). Furthermore, the HC-10 defined epitope appears to be involved in the pathogenesis of spondyloarthropathies, because HC-10 reduced their incidence in HLA-B27(+)beta(2)m degrees /MHC class II knockout mice. This study has characterized the determinant recognized by HC-10. Panning of a phage display peptide library with HC-10 resulted in isolation of the motif PxxWDR, which could be aligned with P57, W60, D61, and R62 of the first domain of the HLA-I HC allospecificities reactive with HC-10. The (55)EGPEYWDR(N/E)T(64) (p-1) is the shortest motif-bearing peptide that reacts with HC-10 and inhibits its binding to soluble HLA-B7 HC, irrespective of whether N (p-1a) or E (p-1b) is present at position 63. By contrast, HC-10 did not react with six additional peptides, each bearing motif amino acid substitutions present in HC-10-not-reactive HLA-I allospecificities. The p-1-derived Qp-1, synthesized with the additional conserved Q54, which displays the highest in vitro reactivity with HC-10, was the only one to induce in mice IgG resembling HC-10 in their fine specificity. Mapping of the HC-10-defined determinant suggests that the lack of mAb reactivity with beta(2)m-associated HLA-I HC is caused by blocking by the peptide in the groove of beta(2)m-associated HLA-I HC, though a role of HC conformational changes following its association with beta(2)m cannot be excluded. This information contributes to our understanding of the molecular basis of the antigenic profiles of beta(2)m-free and beta(2)m-associated HLA-I HC and may serve to develop active specific immunotherapy of spondyloarthropathies.     

Snake bites accidents in Yopal and Leticia, Colombia, 1996-1997

Snakebites produce notable morbidity and mortality in the Amazonian and Orinocan regions of Colombia. A review was undertaken of 56 snakebite cases sent to hospitals in Leticia (Amazonas) and Yopal (Casanare) between September 1996 and June 1997. Of the total, 57% of the bites occurred in Leticia, 54% in men. The 14 to 44 year-old age group was most compromised (41%). Most encounters occurred in forests and open fields between 17:00 and 18:00 hours (57%). Nearly all bites were located on legs and feet (82%). One death occurred in Yopal; 3 fasciotomies and 2 amputations were performed. Snakebite incidence occurred with highest probability during evening hours. Although antibiotics are in general use, minor infections (16%) were frequent.     

A zebrafish orthologue (whnb) of the mouse nude gene is expressed in the epithelial compartment of the embryonic thymic rudiment

The cloning and characterization of the zebrafish orthologue of the mouse nude (Whn/Foxn1) gene, whnb are reported. A previously described Whn-like gene from zebrafish, now designated as whna, is shown to be the orthologue of the mouse Foxn4 gene. The whnb gene is specifically expressed in the thymic rudiment of zebrafish embryos at day 3 after fertilization, whereas the whna gene is expressed in eye and brain structures. Whnb expression is maintained in cloche mutants, where endothelial and haematopoietic cell differentiation is defective, but absent in casanova mutants where endoderm formation is impaired. In adult thymi, whnb is expressed throughout cortical and medullary areas, whereas whna expression is observed in rare cell clusters only. Our results provide the first specific marker for the epithelial compartment of the zebrafish thymus.     

Possible role of glutamate, aspartate, glutamine, GABA or taurine on cadmium toxicity on the hypothalamic pituitary axis activity in adult male rats

This work was designed to evaluate the possible changes in glutamate, aspartate, glutamine, GABA and taurine within various hypothalamic areas the striatum and prefrontal cortex after oral cadmium exposure in adult male rats, and if these changes are related to pituitary hormone secretion. The contents of glutamine, glutamate, aspartate, GABA and taurine in the median eminence, anterior, mediobasal and posterior hypothalamus, and in prefrontal cortex in adult male rats exposed to 272.7 mol l^–1 of cadmium chloride (CdCl₂) in the drinking water for one month. Cadmium diminished the content of glutamine, glutamate and aspartate in anterior hypothalamus as compared to the values found in the untreated group. Besides, there is a decrease in the content of glutamate, aspartate and taurine in the prefrontal cortex. The amino acids studied did not change in median eminence, mediobasal and posterior hypothalamus or the striatum by cadmium treatment. Plasma prolactin and LH levels decreased in rats exposed to the metal. These results suggest that (1) cadmium differentially affects amino acid content within the brain region studied and (2) the inhibitory effect of cadmium on prolactin and LH secretion may be partially explained by a decrease in the content of both glutamate and aspartate in anterior hypothalamus, but not through changes in GABA and taurine.