Estimation of the mutagenic potential of the trematode Opisthorchis felineus in experimentally infected guinea pigs

We studied the mutagenic potential of the trematode Opisthorchis felineus in experimentally infected guinea pigs by chromosome analysis. The investigation was conducted on 30 treated (experimentally infected) and 20 normal (uninfected) guinea pigs (Cavia porcellus). A sample of living metacercariae of O. felineus was obtained from the muscle of naturally infected crucian carp captured in the Tom River, and 1 ml suspension containing approximately 50 metacercariae in 0.9% NaCl solution was individually given p.o. to guinea pigs that were used as treated specimens, whereas normal guinea pigs from the same stock were given 1 ml 0.9% NaCl solution per individual to serve as controls. The treated and control animals were killed by CO2 asphyxiation and decapitation at 7, 15, 30, 45, and 120 days after contamination. The smears of bone marrow cells for chromosome analysis were prepared by a standard method. Statistical analysis of the data was done using Student's t-test. We found that experimental infection of guinea pigs with O. felineus induced significantly high frequencies of hypoploid cells and, at the 120th day p.i., led to a considerable incidence of chromatid breaks and polyploidy in bone marrow cells.     

Radicicol leads to selective depletion of Raf kinase and disrupts K-Ras-activated aberrant signaling pathway

Activation of Ras leads to the constitutive activation of a downstream phosphorylation cascade comprised of Raf-1, mitogen-activated protein kinase (MAPK) kinase, and MAPK. We have developed a yeast-based assay in which the Saccharomyces cerevisiae mating pheromone-induced MAPK pathway relied on co-expression of K-Ras and Raf-1. Radicicol, an antifungal antibiotic, was found to inhibit the K-ras signaling pathway reconstituted in yeast. In K-ras-transformed, rat epithelial, and K-ras-activated, human pancreatic carcinoma cell lines, radicicol inhibited K-Ras-induced hyperphosphorylation of Erk2. In addition, the level of Raf kinase was significantly decreased in radicicol-treated cells, whereas the levels of K-Ras and MAPK remained unchanged. These results suggest that radicicol disrupts the K-Ras-activated signaling pathway by selectively depleting Raf kinase and raises the possibility that pharmacological destabilization of Raf kinase could be a new and powerful approach for the treatment of K-ras-activated human cancers.     

A light-scattering spectrometer for medical diagnostic tasks

Whether a high-resolving light scattering spectrometer may be used in medical practice is discussed in the paper. The results of the experiments on blood components and microorganisms are discussed.     

'Tunable' positive and negative surface charges on a capillary wall: exploiting the Immobiline chemistry

The Immobiline (weak acrylamido acids and bases) chemistry has been applied to the covalent attachment of a positively (or, if needed, negatively) charged layer onto the inner surface of the silica wall. In particular, the following basic Immobilines have been used: pK 6.2, pK 7.0, pK 8.5 and pK 9.3. In order to avoid pK changes, the charged Immobilines are mixed with neutral acrylamido derivatives (in particular the highly resistant and hydrophilic N-acryloyl aminoethoxyethanol) so as to form a co-polymer having a 1:5 molar ratio (charged to neutral). The mu(eo) vs. pH curves have a slope opposite to that of a naked capillary and fan out on the pH scale following the titration curves of the different weak bases. Such chemistry allows the covalent attachment of charged species having known pK values and offering controlled charged densities on the wall. However, with the atomic force microscope, it is found that such soft coatings (whether charged or neutral) do not seem to provide complete coverage of the surface: naked patches of fused silica are found interdispersed among the polymer-coated ones. A good solution is a hybrid bonded and dynamic coating, obtained by adding short chain linear polyacrylamides to the background electrolyte. Good separations of polycations [poly(L-histidine)] and of histones are reported up to pH 5.7.     

Subchronic oral hepatotoxicity of turmeric in mice--histopathological and ultrastructural studies

OBJECTIVE: To analyze the effects of flutamide in patients with physical and/or mental disorders consulting for urinary symptoms secondary to benign prostatic hyperplasia (BPH). METHODS: 50 patients with BPH in whom surgical treatment was contraindicated due to their physical and/or mental condition were treated with flutamide 250 mg/day. Four patients presented with urinary retention and 46 patients had prostatic symptomatology. Patients were evaluated using the symptoms score (I-PSS) and quality of life (QL). Prostate volume was measured by transabdominal US; the maximum flow rate at spontaneous micturition and residual urine were determined. RESULTS: At 12 months, the I-PSS and QL scores decreased by a mean of 7 and 3 points, respectively. The US demonstrated that treatment had reduced prostatic volume by a mean of 10 gms. The maximum flow rate at spontaneous micturition increased 3 ml/sec and residual urine decreased by 15 ml. CONCLUSION: Flutamide is another alternative to surgery in specific patients with BPH.     

An oxazine reagent for derivatization of carboxylic acid analytes suitable for liquid chromatographic detection using visible diode laser-induced fluorescence

This study reports the use of Nile Blue, an oxazine dye, as a derivatization reagent that fluoresces in the far-red spectral region and is suitable for derivatization with carboxylic-acid-containing analytes. Model carboxylic acid analytes such as benzoic acid, acetic acid, phenylacetic acid and hexanoic acid have been reacted as acid chlorides to form Nile Blue derivatives. The synthesis product of the Nile Blue benzoic acid derivative was confirmed using electrospray-mass spectrometry, infrared spectrometry, 1H and 13C nuclear magnetic resonance, reversed phase liquid chromatography (RP-HPLC), normal phase-thin layer chromatography, and spectral characterization. The synthesized Nile Blue derivatives, separated from reaction by-products with RP-HPLC, all demonstrated an approximately 10-fold drop in molar absorptivity and relative quantum yield. In addition, a 40 nm increase in Stokes shift was observed. A portion of the fluorescence was regained through post-column ionization of the Nile Blue benzoic acid derivative at pH 12. A RP-HPLC limit of detection of 88.25 fmol on column has been reported with conventional fluorescence detection-post-column ionization of the Nile Blue benzoic acid derivative. A limit of detection of 1.99 fmol on column (3.98 x 10(-11) M) has been demonstrated for the Nile Blue benzoic acid derivative with the use of a laboratory-constructed visible diode laser fluorescence detector.     

Stress increases the population of splenic macrophages, permissive for Langat virus, in mice

Cytogenetic study conducted after a single intraperitoneal injection of cyclophosphane in doses of 10, 20, and 40 mg/kg showed in 1.5-2-month-old male mice that the level of bone marrow cells damaged by the mutagen was significantly higher in NZW animals than in C57Bl/6 animals. The ability to produce active oxygen forms in response to addition of opsonized zymosan and phorbol myristate acetate was also higher in bone marrow suspensions of NZW mice. The higher sensitivity of NZW animals to pro-oxidant and clastogenic effects may be related to the genetically determined decrease of antioxidant protection in NZW animals.     

Conduct disorder with and without mania in a referred sample of ADHD children

OBJECTIVE: To test the hypothesis that dysphoric and non-dysphoric types of CD could be distinguished from one another in their patterns of familiality, adversity, and comorbidity. METHODS: We examined 140 ADHD and 120 normal controls at baseline and 4 years later using assessments from multiple domains. We compared ADHD subgroups with and without conduct (CD) and bipolar (BPD) disorders on psychiatric outcomes at a 4-year follow-up, familial psychopathology and psychosocial functioning. RESULTS: We found that ADHD children with both disorders had higher familial and personal risk for mood disorders than those with CD only, who had a higher personal risk for antisocial personality disorder. Among ADHD probands, having both CD and BPD was associated with poorer functioning and an increased risk for psychiatric hospitalization. DISCUSSION: Although preliminary, our findings suggest that the distinction between dysphoric and non-dysphoric CD may be clinically meaningful. If confirmed, our findings could have important diagnostic and therapeutic implications for the management of antisocial youth.     

Distinct roles of the interleukin-7 receptor alpha chain in fetal and adult thymocyte development revealed by analysis of interleukin-7 receptor alpha-deficient mice

Mouse mutants lacking expression of the IL-7 receptor (IL-7R) alpha chain are defective in thymopoiesis. The adult thymus has multiple defects, including reduced cell numbers and proportions of the more mature thymocyte subsets, a complete absence of CD25+ cells and a reduced level of RAG1 and RAG2 expression. We show here that, in contrast to the profound developmental arrest observed in the adult thymus, fetal thymocytes from IL-7Ralpha-/- mice have normal proportions of all of the major thymocyte subpopulations, including CD25+ thymocytes and the most mature single-positive subsets. Moreover, normal levels of RAG1 and RAG2 were observed. Total thymocyte numbers, however, remained reduced. These data suggest that the IL-7Ralpha chain is a key regulator of both survival and proliferation during thymocyte development but that it is not essential for the production of T cells during fetal thymopoiesis.