973. DENDROBIUM HEKOUENSE

Dendrobium hekouense Z.J. Liu & L.J. Chen is illustrated. Its distribution, ecology and successful cultivation are described.     

Loss of Acid Sensing Ion Channel-1a and Bicarbonate Administration Attenuate the Severity of Traumatic Brain Injury

Traumatic brain injury (TBI) is a common cause of morbidity and mortality in people of all ages. Following the acute mechanical insult, TBI evolves over the ensuing minutes and days. Understanding the secondary factors that contribute to TBI might suggest therapeutic strategies to reduce the long-term consequences of brain trauma. To assess secondary factors that contribute to TBI, we studied a lateral fluid percussion injury (FPI) model in mice. Following FPI, the brain cortex became acidic, consistent with data from humans following brain trauma. Administering HCO₃ ⁻ after FPI prevented the acidosis and reduced the extent of neurodegeneration. Because acidosis can activate acid sensing ion channels (ASICs), we also studied ASIC1a^−/− mice and found reduced neurodegeneration after FPI. Both HCO₃ ⁻ administration and loss of ASIC1a also reduced functional deficits caused by FPI. These results suggest that FPI induces cerebral acidosis that activates ASIC channels and contributes to secondary injury in TBI. They also suggest a therapeutic strategy to attenuate the adverse consequences of TBI.     

The potential value of CA125 as a tumour marker in small volume, non-evaluable epithelial ovarian cancer.

Seventy four consecutive patients with epithelial ovarian cancer have been followed up longitudinally with serial serum CA125 for up to 48 months. From this database, the CA125 changes in small volume disease have been evaluated. For long term complete responders (n = 12), the mean plateau level of CA125 was 7.2 U/ml (95% confidence interval; 5.6 to 9.2 U/ml). The natural half-life of CA125 at 5.1 days (range 3.8 to 7 days) was calculated from five patients with Stage I and II disease who underwent complete surgical excision. A mean lead time of 99 days (range 14 to 255 days) was demonstrated between marker detection of disease progression and clinically apparent progressive disease in 12 out of 13 patients (92%) who relapsed after chemotherapy induced complete remission. The threshold of tumour volume detection with CA125 is unlikely to be determined by an arbitrary cut-off level. The kinetics of CA125 provide more useful information and the potential to define complete response or indeed cure with CA125 parameters requires further investigation.     

Ecology of a saline stream: community responses to spatial gradients of environmental conditions

Spatial changes in structural and functional characteristics of fish and macroinvertebrate communities in eastern Kentucky were investigated in a drainage system chronically exposed to high levels of chloride salts from nearby oilfield operations. Salinity levels at biological monitoring stations ranged from 0.12–31.3‰. Lotic regions with salinities greater than 10‰ were dominated by larvae of the dipterans Ephydra and Culicoides. In regions with salinities less than 10‰ species richness increased more or less linearly with decreasing levels of chloride salts. Ephemeropterans appeared to be one of the major invertebrate groups least tolerant of elevated NaCl levels and were absent in regions with salinities greater than 2‰ Availability of food resources, such as periphyton and particulate organic matter, did not appear to be grossly altered in disturbed regions, and it is suggested that the observed distribution of macroinvertebrate fauna was largely in response to taxonomic differences in salt tolerance. Fish seemed to be more tolerant of highly saline conditions, and several species were observed in regions experiencing salinities as high as 15‰. Accordingly, assemblages of fish taxa along the salinity gradient may have been influenced by trophic factors, such as spatial limitations in availability of invertebrate prey.     

High-Frequency Stimulation of Excitable Cells and Networks

High-frequency (HF) stimulation has been shown to block conduction in excitable cells including neurons and cardiac myocytes. However, the precise mechanisms underlying conduction block are unclear. Using a multi-scale method, the influence of HF stimulation is investigated in the simplified FitzhHugh-Nagumo and biophysically-detailed Hodgkin-Huxley models. In both models, HF stimulation alters the amplitude and frequency of repetitive firing in response to a constant applied current and increases the threshold to evoke a single action potential in response to a brief applied current pulse. Further, the excitable cells cannot evoke a single action potential or fire repetitively above critical values for the HF stimulation amplitude. Analytical expressions for the critical values and thresholds are determined in the FitzHugh-Nagumo model. In the Hodgkin-Huxley model, it is shown that HF stimulation alters the dynamics of ionic current gating, shifting the steady-state activation, inactivation, and time constant curves, suggesting several possible mechanisms for conduction block. Finally, we demonstrate that HF stimulation of a network of neurons reduces the electrical activity firing rate, increases network synchronization, and for a sufficiently large HF stimulation, leads to complete electrical quiescence. In this study, we demonstrate a novel approach to investigate HF stimulation in biophysically-detailed ionic models of excitable cells, demonstrate possible mechanisms for HF stimulation conduction block in neurons, and provide insight into the influence of HF stimulation on neural networks.     

Synthesis and Biological Evaluation of Dideoxunucleosides Containing A Difluoromethylene Unit

Abstract

2′-difluoro and 3′-difluoro dideoxynucleosides containing thymine and cytosine as the base were synthesized. These compounds inhibited HeLa cell growth and Moloney leukemia virus to a modest degree.     

A fungal endophyte defensive symbiosis affects plant-nematode interactions in cotton

Background and aims

Most investigations of fungi as nematode antagonists have focused on their interactions with nematodes in the soil. This study tested a foliar-isolated endophytic Phialemonium inflatum for its effects against the root-knot nematode as an endophyte in cotton using a seed treatment inoculation.

Methods

Cotton seeds were inoculated with P. inflatum spore suspensions prior to planting. Nematode infection and reproduction were quantified at Day 12 and 6 weeks after nematode egg inoculation, respectively. To establish whether the observed negative effects on nematodes were due to P. inflatum in the soil or as an endophyte in the plant, we also applied a soil fungicide treatment at the seedling stage to kill the fungi outside the plant.

Results

Persistent suppression of nematode penetration and galling, as well as subsequent reproduction, were observed in endophyte-treated plants independent of fungicide treatment, consistent with an endophytic mode of nematode suppression; and these negative effects did not depend on the concentration of fungal inoculum used to treat to the seed.

Conclusions

Our study highlights a novel role for P. inflatum as part of a plant-fungal defensive symbiosis in cotton, as well as the need for a broader understanding of endophyte-plant-nematode ecological interactions.

     

Long‐term trends in restoration and associated land treatments in the southwestern United States

Restoration treatments, such as revegetation with seeding or invasive species removal, have been applied on U.S. public lands for decades. Temporal trends in these management actions have not been extensively summarized previously, particularly in the southwestern United States where invasive plant species, drought, and fire have altered dryland ecosystems. We assessed long‐term (1940–2010) trends in restoration using approximately 4,000 vegetation treatments conducted on Bureau of Land Management lands across the southwestern United States. We found that since 1940, the proportions of seeding and vegetation/soil manipulation (e.g. vegetation removal or plowing) treatments have declined, while the proportions of prescribed burn and invasive species treatments have increased. Treatments in pinyon‐juniper and big sagebrush communities declined in comparison to treatments in desert scrub, creosote bush, and riparian woodland communities. Restoration‐focused treatment objectives increased relative to resource extraction objectives. Species richness and proportion of native species used in seeding treatments also increased. Inflation‐adjusted costs per area rose 750% for vegetation/soil manipulation, 600% for seeding, and 400% for prescribed burn treatments in the decades from 1981 to 2010. Seeding treatments were implemented in warmer and drier years when compared to the climate conditions of the entire study period and warmer and wetter years relative to several years before and after the treatment. These results suggest that treatments over a 70‐year period on public lands in the southwestern United States are shifting toward restoration practices that are increasingly large, expensive, and related to fire and invasive species control.     

Co-Processed Excipients for Dispersible Tablets–Part 1: Manufacturability

Co-processed excipients may enhance functionality and reduce drawbacks of traditional excipients for the manufacture of tablets on a commercial scale. The following study aimed to characterise a range of co-processed excipients that may prove suitable for dispersible tablet formulations prepared by direct compression. Co-processed excipients were lubricated and compressed into 10.5-mm convex tablets using a Phoenix compaction simulator. Compression profiles were generated by varying the compression force applied to the formulation and the prepared tablets were characterised for hardness, friability, disintegration and fineness of dispersion. Our data indicates that CombiLac, F-Melt type C and SmartEx QD100 were the top 3 most suitable out of 16 co-processed excipients under the conditions evaluated. They exhibited good flow properties (Carr’s index ? 20), excellent tabletability (tensile strength >?3.0 MPa at 0.85 solid fraction), very low friability (<?1% after 15 min), rapid disintegration times (27–49 s) and produced dispersions of ideal fineness (<?250 μm). Other co-processed excipients (including F-Melt type M, Ludiflash, MicroceLac, Pharmaburst 500 and Avicel HFE-102) may be appropriate for dispersible tablets produced by direct compression providing the identified disintegration and dispersion risks were mitigated prior to commercialisation. This indicates that robust dispersible tablets which disintegrate rapidly could be manufactured from a range of co-processed excipients.