Synthesis of Novel 4′-Trifluoromethyl-5′-Norcarbocyclic C-Nucleoside Phosphonic Acids as Potent Anti-Leukemic Agents

The syntheses of novel C-nucleoside phosphonic acids as potential antiviral agents are described. The sugar moiety that served as the nucleoside skeleton was produced starting from commercially available 1,3-dihydroxy cyclopentane. The key C-C bond formation from sugar to base precursor was performed using the Knoevenagel-type condensation. The synthesized compounds exhibited anti-HIV activity and cytotoxicity. Also, the synthesized compounds were screened in vitro for tumor growth inhibitory activity against mouse leukemia cell lines (L-1210, P-815).     

A salt on the bioenergy and biological invasions debate: salinity tolerance of the invasive biomass feedstock Arundo donax

Arundo donax L., commonly known as giant reed, is promising biomass feedstock that is also a notorious invasive plant in freshwater ecosystems around the world. Heretofore, the salt tolerance of A. donax had not been quantified even though anecdotal evidence suggests halophytic qualities. To test whole-plant and leaf level responses, we established a pot experiment on 80 scions propagated from an A. donax population that has naturalized on the shore of the San Francisco Bay Estuary. To quantify growth and physiological responses to salinity (NaCl), A. donax scions were divided into eight treatments and grown for 60 days across a range of salinities (0–42 dS m⁻¹). Classic growth analysis showed >80% reduction in overall growth at the highest salinities. Yet, there was zero mortality indicating that A. donax is able to tolerate high levels of salt. Declining photosynthesis rates were strongly correlated (R² > 0.97) with decreasing stomatal conductance, which was in turn closely related to increasing salinity. Leaf gas exchange revealed that stomata and leaf limitations of carbon dioxide were three times greater at high salinities. Nonetheless, even when salinities were 38–42 dS m⁻¹ A. donax was able to maintain assimilation rates 7–12 μmol m⁻² s⁻¹. Further, by maintaining 50% relative growth at salinities ~12 dS m⁻¹ A. donax can now be classified as ‘moderately salt tolerant’. A. donax leaf gas exchange and whole-plant salt tolerance are greater than many important food crops (i.e. maize, rice), the bioenergy feedstock Miscanthus × giganteus, as well as some uncultivated plant species (i.e. Populus and Salix) that are indigenous in regions A. donax currently invades. The results of this study have implications for both agronomists wishing to expand A. donax to fields dominated by saline soils, and for others who are concerned about the spread of A. donax with altered stream hydrology or sea-level rise.     

Can Inconsistent Association between Hypertension and Cognition in Elders be Explained by Levels of Organochlorine Pesticides?

The relation between hypertension and cognition in elders remains unclear, and studies on the effect of antihypertensive drugs on cognition have demonstrated conflicting results. This study was performed to evaluate if the association between hypertension and cognition in elders differed depending on serum concentrations of organochlorine (OC) pesticides, common neurotoxic chemicals. Participants were 644 elders aged 60–85 years who participated in the National Health and Nutrition Examination Survey 1999–2002 and were able to complete a cognitive test. We selected 6 OC pesticides that were commonly detected in the elderly. Cognition was assessed by the Digit Symbol Substitution Test (DSST), a relevant tool for evaluating hypertension-related cognitive function, and low cognition was defined by the DSST score < 25^th percentile. When OC pesticides were not considered in the analyses, elders with hypertension had about 1.7 times higher risk of low cognition than those without hypertension. However, in analyses stratified by serum concentrations of OC pesticides, the associations between hypertension and low cognition were stronger the higher the serum concentrations of p,p’-DDT, p,p’-DDE, β-hexachlorocyclohexane, and trans-nonachlor increased. Among elders in the 3^rd tertile of these pesticides, adjusted odds ratios were from 2.5 to 3.5. In contrast, hypertension was not clearly associated with the risk of low cognition in elders in the 1^st tertile of these pesticides. Similar patterns were observed for the continuous DSST score dependent variable. The difference in the association between hypertension and DSST scores according to the levels of OC pesticides suggest a key role of OC pesticides in the development of hypertension-related cognitive impairment and may help to identify hypertensive elders who are at a high risk of cognitive impairment.     

2-(Trimethylammonium) Ethyl (R)-3-Methoxy-3-oxo-2-Stearamidopropyl Phosphate Suppresses Osteoclast Maturation and Bone Resorption by Targeting Macrophage-Colony Stimulating Factor Signaling

2-(Trimethylammonium) ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl phosphate [(R)-TEMOSPho], a derivative of an organic chemical identified from a natural product library, promotes highly efficient megakaryopoiesis. Here, we show that (R)-TEMOSPho blocks osteoclast maturation from progenitor cells of hematopoietic origin, as well as blocking the resorptive function of mature osteoclasts. The inhibitory effect of (R)-TEMOSPho on osteoclasts was due to a disruption of the actin cytoskeleton, resulting from impaired downstream signaling of c-Fms, a receptor for macrophage-colony stimulating factor linked to c-Cbl, phosphoinositol-3-kinase (PI3K), Vav3, and Rac1. In addition, (R)-TEMOSPho blocked inflammation-induced bone destruction by reducing the numbers of osteoclasts produced in mice. Thus, (R)-TEMOSPho may represent a promising new class of antiresorptive drugs for the treatment of bone loss associated with increased osteoclast maturation and activity.     

Heavy Hymenolepis nana Infection Possibly Through Organic Foods: Report of a Case

We encountered a patient with heavy Hymenolepis nana infection. The patient was a 44-year-old Korean man who had suffered from chronic hepatitis (type B) for 15 years. A large number of H. nana adult worms were found during colonoscopy that was performed as a part of routine health screening. The parasites were scattered throughout the colon, as well as in the terminal ileum, although the patient was immunocompetent. Based on this study, colonoscopy may be helpful for diagnosis of asymptomatic H. nana infections.