Changes in body size of newborns in Lithuania, 1974-2004

The purpose of this study was to analyse body size of Lithuanian newborns born in 1998 and 2004, and to compare results with the data from 1974. The main body size measurements - body weight, body length and body mass index (BMI) of 3281 (1705 boys and 1576 girls) live term singleton Lithuanian newborns' were analysed according to gestational age, sex and health status. The data were collected in the Clinic of Obstetrics and Gynaecology of Vilnius University (VU COG), and the comparison with the data of Lithuanian Medical Birth Register of (LMBR) was performed. No significant differences between height, weight and body mass index in 1998 and the same characteristics in 2004 were observed. Means and principal percentiles (10th, 50th, 90th) of body measurements of 37-42 weeks of gestational age newborns were obtained. The mean body length was 52.8/52.19 cm (boys/girls), body weight--3589/3454 g, BMI 12.82/12.64 correspondingly. The recent data were compared with the similar data from 1974 cohort. Statistically significant increment of body length of Lithuanian newborns was observed in all age and sex groups, whereas weight changes were less evident. The analysis of BMI demonstrated the following trend: newborns became longer, but not relatively heavier in comparison with the similar data 30 years ago. Hence, it is important to evaluate weight changes of neonate in relation with the changes in height. Further investigation of prevalence of neonatal macrosomia, possible factors of body size changes, their relationship to general health status and further health issues of the child should be explored.     

Evolution of the clinical presentation and outcomes after radical prostatectomy for patients with clinically localized prostate cancer--changing trends over a ten year period

We demonstrate the evolution of the clinical presentation and outcomes for patients with clinically localized prostate cancer (PC) treated with radical retropubic prostatectomy (RRP) at our department, emphasizing epidemiologic significance of changes during the 10-year period. We assessed the annual trends for changes in patients age, preoperative prostate specific antigen (PSA), preoperative versus postoperative stages and Gleason grades, organ confined status and surgical margin status. A total of 488 RRPs were performed from January 1996 to December 2005 with the annual frequency increased from 8 to 129 (1512.5%). Mean patient age increased from 61.5 to 66.12 years in 2005, with the percentage of men aged more than 70 years increased from 12.5 to 26.5%, respectively. The detection of PC based solely on pathological PSA levels (as indication for prostate biopsy) rose impressively from 25.5 to 70% and the rates of postoperative organ-confined disease also increased significantly from 25 to 74.7%. Mean preoperative PSA decreased from 16.7 to 9.89 ng/mL. On the contrary, there was an increase in percentage of patients with preoperative PSA values ranging from 4 to 10 ng/mL (from 20 to 65.4%). Positive surgical margin rate decreased from 49.4 to 25% and percent of patients receiving neoadjuvant therapy decreased from 78.5 to 5.4%. Proportion of patients who were undergraded decreased from 75.1 to 31.7%. The rates of understaging have remained relatively stable over the years. During the study period, PC was increasingly detected by prostate biopsy on the basis of a pathological PSA level only and shifted significantly to more organ-confined stages with more favourable outcomes for pathological variables due to a more accurate assessment of clinical stage prior to surgery, reduced use of neoadjuvant therapy and improved surgical technique. Our data also argue strongly that routine PSA testing should be expanded and not restricted.     

Molecular characterization of strawberry pathogen Gnomonia fragariae and its genetic relatedness to other Gnomonia species and members of Diaporthales

Gnomonia fragariae is a poorly studied ascomycete belonging to Diaporthales. Originally G. fragariae was considered a saprophyte occurring on dead tissues of strawberry plants. Recently this fungus was found in Latvia and Sweden, and it was proven to be the cause of severe root rot and petiole blight of strawberry. Thirteen isolates of this pathogen and several other Gnomonia species occurring on rosaceous hosts were characterized by molecular analysis using nucleotide sequences of partial LSU rRNA gene and the total ITS region. The homologous regions from relevant diaporthalean taxa available in the GenBank were also included and compared with the taxa sequenced in this study. Phylogenetic analyses revealed that G. fragariae, G. rubi, and Gnomonia sp. (CBS 850.79) were genetically different from G. gnomon, the type species of the genus, and other members of Gnomoniaceae. The analyses showed that G. fragariae and Hapalocystis were genetically very closely related, forming a phylogenetic clade, which is possibly presenting a new family in the Diaporthales. Morphological comparisons of the Gnomonia species on the basis of commonly used criteria for the taxonomy of Diaporthales, so far did not reveal any evident features for the polyphyletic status of Gnomonia.     

Discovery of 5-HT6 receptor ligands based on virtual HTS

Based on a pharmacophore alignment on a 5-HT(6) ligand applying 4SCan technology, a new lead series was identified and further structurally investigated. K(i)s down to 8 nM were achieved.     

Patterns of male reproductive success in a highly promiscuous whale species: the endangered North Atlantic right whale

Parentage analyses of baleen whales are rare, and although mating systems have been hypothesized for some species, little data on realized male reproductive success are available and the patterns of male reproductive success have remained elusive for most species. Here we combine over 20 years of photo-identification data with high-resolution genetic data for the majority of individual North Atlantic right whales to assess paternity in this endangered species. There was significant skew in male reproductive success compared to what would be expected if mating was random (P < 0.001). The difference was due to an excess of males assigned zero paternities, a deficiency of males assigned one paternity, and an excess of males assigned as fathers for multiple calves. The variance in male reproductive success was high relative to other aquatically mating marine mammals, but was low relative to mammals where the mating system is based on resource- and/or mate-defence polygyny. These results are consistent with previous data suggesting that the right whale mating system represents one of the most intense examples of sperm competition in mammals, but that sperm competition on its own does not allow for the same degree of polygyny as systems where males can control access to resources and/or mates. The age distribution of assigned fathers was significantly biased towards older males (P < 0.05), with males not obtaining their first paternity until approximately 15 years of age, which is almost twice the average age of first fertilization in females (8 years), suggesting that mate competition is preventing younger males from reproducing. The uneven distribution of paternities results in a lower effective population size in this species that already has one of the lowest reported levels of genetic diversity, which may further inhibit reproductive success through mate incompatibility of genetically similar individuals.     

Impact of vCJD on blood supply.

Variant Creutzfeldt-Jakob disease (vCJD) is an at present inevitably lethal neurodegenerative disease which can only be diagnosed definitely post mortem. The majority of the approximately 200 victims to date have resided in the UK where most contaminated beef materials entered the food chain. Three cases in the UK demonstrated that vCJD can be transmitted by blood transfusion. Since BSE and vCJD have spread to several countries outside the UK, it appears advisable that specific risk assessments be carried out in different countries and geographic areas. This review explains the approach adopted by Germany in assessing the risk and considering precautionary measures. A fundamental premise is that the feeding chain of cattle and the food chain have been successfully and permanently cleared from contaminated material. This raises the question of whether transmissions via blood transfusions could have the potential to perpetuate vCJD in mankind. A model calculation based on actual population data showed, however, that this would not be the case. Moreover, an exclusion of transfusion recipients from blood donation would add very little to the safety of blood transfusions, but would have a considerable impact on blood supply. Therefore, an exclusion of transfusion recipients was not recommended in Germany.     

Hydrogen sulfide mediates vasoactivity in an O2-dependent manner

Hydrogen sulfide (H(2)S) has recently been shown to have a signaling role in vascular cells. Similar to nitric oxide (NO), H(2)S is enzymatically produced by amino acid metabolism and can cause posttranslational modification of proteins, particularly at thiol residues. Molecular targets for H(2)S include ATP-sensitive K(+) channels, and H(2)S may interact with NO and heme proteins such as cyclooxygenase. It is well known that the reactions of NO in the vasculature are O(2) dependent, but this has not been addressed in most studies designed to elucidate the role of H(2)S in vascular function. This is important, since H(2)S reactions can be dramatically altered by the high concentrations of O(2) used in cell culture and organ bath experiments. To test the hypothesis that the effects of H(2)S on the vasculature are O(2) dependent, we have measured real-time levels of H(2)S and O(2) in respirometry and vessel tension experiments, as well as the associated vascular responses. A novel polarographic H(2)S sensor developed in our laboratory was used to measure H(2)S levels. Here we report that, in rat aorta, H(2)S concentrations that mediate rapid contraction at high O(2) levels cause rapid relaxation at lower physiological O(2) levels. At high O(2), the vasoconstrictive effect of H(2)S suggests that it may not be H(2)S per se but, rather, a putative vasoactive oxidation product that mediates constriction. These data are interpreted in terms of the potential for H(2)S to modulate vascular tone in vivo.     

Large-conductance calcium-activated potassium channel activity is absent in human and mouse neutrophils and is not required for innate immunity

Large-conductance Ca²⁺-activated K⁺ (BK) channels are reported to be essential for NADPH oxidase-dependent microbial killing and innate immunity in leukocytes. Using human peripheral blood and mouse bone marrow neutrophils, pharmacological targeting, and BK channel gene-deficient (BK^–/–) mice, we stimulated NADPH oxidase activity with 12-O-tetradecanoylphorbol-13-acetate (PMA) and performed patch-clamp recordings on isolated neutrophils. Although PMA stimulated NADPH oxidase activity as assessed by O₂^– and H₂O₂ production, our patch-clamp experiments failed to show PMA-activated BK channel currents in neutrophils. In our studies, PMA induced slowly activating currents, which were insensitive to the BK channel inhibitor iberiotoxin. Instead, the currents were blocked by Zn²⁺, which indicates activation of proton channel currents. BK channels are gated by elevated intracellular Ca²⁺ and membrane depolarization. We did not observe BK channel currents, even during extreme depolarization to +140 mV and after elevation of intracellular Ca²⁺ by N-formyl-L-methionyl-L-leucyl-phenylalanine. As a control, we examined BK channel currents in cerebral and tibial artery smooth muscle cells, which showed characteristic BK channel current pharmacology. Iberiotoxin did not block killing of Staphylococcus aureus or Candida albicans. Moreover, we addressed the role of BK channels in a systemic S. aureus and Yersinia enterocolitica mouse infection model. After 3 and 5 days of infection, we found no differences in the number of bacteria in spleen and kidney between BK^–/– and BK^+/+ mice. In conclusion, our experiments failed to identify functional BK channels in neutrophils. We therefore conclude that BK channels are not essential for innate immunity. killing assay; reactive oxygen species; BK-deficient mice; mice infection     

Radiolabeled peptides and proteins in cancer therapy

With the advances in genomics, molecular biology including gene vector technologies today's molecular imaging modalities have strongly been improved. The major progress is based on peptide and antibody targeting vectors. When labeled with beta(-)-emitting radioisotopes these agents are applicable for endoradiotherapy and exploit the targeting potential for highly specific therapeutic applications. This novel class of pharmaceuticals offers the potential to develop patient specific therapies and might provide the means to go beyond the possibilities of current chemotherapy and radiation therapy. In this review the basic principles of endoradiotherapeutics based on peptides and proteins are presented. Several of these drugs such as (90)Y-rituximab (Zevalin), (131)I-tositumomab (Bexxar) and the somatostatin receptor binding (90)Y-DOTATOC that are nowadays successfully applied in oncological therapy are discussed. Future generations of endoradiopharmaceuticals will address yet unknown targets which might be identified by screening techniques such as ribosome and phage display peptide libraries.