Disk diffusion susceptibility testing of dermatophytes with imidazoles

Flupirtine belongs to the class of triaminopyridines and is successfully applied clinically as a non-opiate analgesic drug with additional muscle relaxant properties. Recently it was reported that flupirtine acts like an antagonist of the N-methyl-D-aspartate (NMDA) receptor complex in neuronal cells both in vitro and in vivo. Here we have used primary cortical cells from rat embryos to demonstrate that this compound is also neuroprotective against the toxic effects caused by the prion agent PrPSc and lead acetate (Pb). These two agents display pleiotropic effects on neurons, which include activation of the NMDA receptor complex. At concentrations above 30 microM the toxic-peptide fragment of PrPSc causes apoptotic fragmentation of DNA and is consequently neurotoxic. Pb is neurotoxic at concentrations above 10 microM. Co-administration of flupirtine (10 microM) with either of these agents resulted in reduced neurotoxicity. These data indicate that the cytoprotective effect of flupirtine is measurable in vitro against these noxious agents which show their effects, including modulation of the NMDA receptor complex, pleiotropically.     

Behavioral, situational, and temporal effects of treatment of ADHD with methylphenidate

OBJECTIVE: To determine the behavioral, situational, and temporal effects of 4 months of methylphenidate (MPH) treatment for attention-deficit hyperactivity disorder (ADHD). METHOD: Ninety-one children with ADHD were randomly assigned to receive either MPH (titrated to a target dose of 0.7 mg/kg twice a day) or a placebo. Treatment effects were investigated with measures sensitive to various behaviors (core and associated symptoms), situations (home and school), time periods (morning and afternoon, after reaching the target dose, and after 4 months of treatment), and side effects. RESULTS: MPH treatment improved symptoms of ADHD and oppositional behavior at school, both in the morning and afternoon, but not at home. Side effects (increase in physiological and effective symptoms, lack of weight gain) were significantly more frequent with MPH than with placebo treatment. Benefit was evident after titration, but the onset of some side effects was delayed. Side effects were reported by parents but not by teachers. CONCLUSIONS: Positive effects of MPH on behavior are evident in the classroom, but with MPH given twice daily, parents do not report that MPH improves behavior at home. Greater impact on home behavior may require three times daily MPH and combined treatments.     

Physiologically based indices of volumetric capnography in patients receiving mechanical ventilation

Several indices of ventilatory heterogeneity can be identified from the expiratory CO2 partial pressure or CO2 elimination versus volume curves. The aims of this study were: 1) to analyse several computerizable indices of volumetric capnography in order to detect ventilatory disturbances; and 2) to establish the relationship between those indices and respiratory system mechanics in subjects with normal lungs and in patients with acute respiratory distress syndrome (ARDS), both receiving mechanical ventilation. We studied six normal subjects and five patients with early ARDS mechanically ventilated at three levels of tidal volume (VT). Respiratory system mechanics were assessed by end-expiratory and end-inspiratory occlusion methods, respectively. We determined Phase III slopes, Fletcher's efficiency index, Bohr's dead space (VD,Bohr/VT), and the ratio of alveolar ejection volume to tidal volume (VAE/VT) from expiratory capnograms, as a function of expired volume. Differences between normal subjects and ARDS patients were significant both for capnographic and mechanical parameters. Changes in VT significantly altered capnographic indices in normal subjects, but failed to change ventilatory mechanics and VAE/VT in ARDS patients. After adjusting for breathing pattern, VAE/VT exhibited the best correlation with the mechanical parameters. In conclusion, volumetric capnography, and, specifically, the ratio of alveolar ejection volume to tidal volume allows evaluation and monitoring of ventilatory disturbances in patients with adult respiratory distress syndrome.     

Interaction of the S phase regulator cdc18 with cyclin-dependent kinase in fission yeast

The fission yeast gene cdc18(+) is required for entry into S phase and for coupling mitosis to the successful completion of S phase. Cdc18 is a highly unstable protein that is expressed only once per cell cycle at the G1/S boundary. Overexpression of Cdc18 causes a mitotic delay and reinitiation of DNA replication, suggesting that the inactivation of Cdc18 plays a role in preventing rereplication within a given cell cycle. In this paper, we present evidence that Cdc18 is associated with active cyclin-dependent kinase in vivo. We have expressed Cdc18 as a glutathione S-transferase fusion in fission yeast and demonstrated that the fusion protein is functional in vivo. We find that the Cdc18 fusion protein copurifies with a kinase activity capable of phosphorylating histone H1 and Cdc18. The activity was identified by a variety of methods as the cyclin-dependent kinase containing the product of the cdc2(+) gene. The amino terminus of Cdc18 is required for association with cyclin-dependent kinase, but the association does not require the consensus cyclin-dependent kinase phosphorylation sites in this region. Additionally, both G1/S and mitotic forms of cyclin-dependent kinase phosphorylate and interact with Cdc18. These interactions between Cdc18 and cyclin-dependent kinases suggest mechanisms by which cyclin-dependent kinases could activate the initiation of DNA replication and could prevent rereplication.     

Mercury in alligators (Alligator mississippiensis) in the southeastern United States

Mercury methylation may be enhanced in wetlands and humic-rich, blackwater systems that crocodiles and alligators typically inhabit. Given their high trophic level and long life-spans, crocodilians could accumulate significant burdens of Hg. Our objectives were to survey Hg concentrations in alligators from several areas in the southeastern United States to test their utility as sentinels of Hg contamination, to examine relationships among Hg concentrations in various tissues and to look for any differences in tissue Hg concentrations among locations. We measured total Hg concentrations in alligators collected in the Florida Everglades (n = 18), the Okefenokee National Wildlife Refuge, Georgia (n = 9), the Savannah River Site (SRS), South Carolina (n = 49) and various locations in central Florida (n = 21), sampling tissues including blood, brain, liver, kidney, muscle, bone, fat, spleen, claws and dermal scutes. Alligators from the Everglades were mostly juvenile, but Hg concentrations in tissues were high (means: liver 41.0, kidney 36.4, muscle 5.6 mg Hg/kg dry wt.). Concentrations in alligators from other locations in Florida were lower (means: liver 14.6, kidney 12.6, muscle 1.8 mg Hg/kg dry wt.), although they tended to be larger adults. Alligators from the Okefenokee were smallest and had the lowest Hg concentrations (means: liver 4.3, kidney 4.8, muscle 0.8 mg Hg/kg dry wt.). SRS alligators had the greatest size range and intermediate Hg levels (means: liver 14.9, muscle 4.8 mg Hg/kg dry wt.). At some locations, alligator length was correlated with Hg concentrations in some internal organs. However, at three of the four locations, muscle Hg was not related to length. Tissue Hg concentrations were correlated at most locations however, claw or dermal scute Hg explained less than 74% of the variation of Hg in muscle or organs, suggesting readily-obtained tissues, such as scutes or claws, have limited value for non-destructive screening of Hg in alligator populations.