The synthesis and identification of 4,6-diaminoquinoline derivatives as potent immunostimulants

The synthesis of a number of 4,6-diaminoquinoline derivatives is described as well as their evaluation in a mouse protection model designed to identify immunostimulant activity. These compounds represent a novel series of potent immunostimulants.     

Correlates of substitution rate variation in mammalian protein-coding sequences

Background  

Rates of molecular evolution in different lineages can vary widely, and some of this variation might be predictable from aspects of species' biology. Investigating such predictable rate variation can help us to understand the causes of molecular evolution, and could also help to improve molecular dating methods. Here we present a comprehensive study of the life history correlates of substitution rate variation across the mammals, comparing results for mitochondrial and nuclear loci, and for synonymous and non-synonymous sites. We use phylogenetic comparative methods, refined to take into account the special nature of substitution rate data. Particular attention is paid to the widespread correlations between the components of mammalian life history, which can complicate the interpretation of results.     

ATP-sensitive K+ channel blocker glibenclamide and diaphragm fatigue during normoxia and hypoxia

The role of ATP-sensitiveK⁺ channels in skeletal musclecontractile performance is controversial: blockers of these channels have been found to not alter, accelerate, or attenuate fatigue. Thepresent study reexamined whether glibenclamide affects contractile performance during repetitive contraction. Experiments systematically assessed the effects of stimulation paradigm, temperature, and presenceof hypoxia and in addition compared intertrain with intratrain fatigue.Adult rat diaphragm muscle strips were studied in vitro. At 37°Cand normoxia, glibenclamide did not significantly affect any measure offatigue during continuous 5- or 100-Hz or intermittent 20-Hzstimulation but progressively prolonged relaxation time during 20-Hzstimulation. At 20°C and normoxia, neither force nor relaxationrate was affected significantly by glibenclamide during 20-Hzstimulation. At 37°C and hypoxia, glibenclamide did notsignificantly affect fatigue at 5-Hz or intertrain fatigue during 20-Hzstimulation but reduced intratrain fatigue and prolonged relaxationtime during 20-Hz stimulation. These findings indicate that, althoughATP-sensitive K⁺ channels may beactivated during repetitive contraction, their activation has only amodest effect on the rate of fatigue development.

     

Determination of volatile products of human colon cell line metabolism by GC/MS analysis

Colon cancer is one of the most reasons for cancer death worldwide. Thus, it is important to find new prognostic and diagnostic marker, as well as to throw light on the special metabolic pathways of colon cancer cells. This paper highlights for the first time some qualitative differences in the profiles of the volatile metabolites of colon cancer cell lines SW 480 (grade IV, Duke B) and SW 1116 (grade II, Duke A) among themselves and in comparison to the normal colon cell line NCM460, which are mostly represented by ketones and alcohols. These results, which were obtained by applying solid phase micro extraction (SPME) and combined gas chromatography/mass spectrometry (GC/MS), are consistent with Warburg’s hypothesis because the found reaction products may indicate that the cancer cells show the Crabtree’s effect. Furthermore, compounds like undecan-2-ol and pentadecan-2-one were associated for the first time with the human metabolism. In summary, these findings indicate that the metabolism of colon cancer cells differs extremely from the metabolism of healthy cells and it changes during the progress of the disease. Compounds that are present in the breath, the blood and the tissue of patients represent the differences and they can serve as new biomarker for colon cancer in future.     

ELECTROKINETICS : XVII. SURFACE CHARGE AND ION ANTAGONISM

1. The question of the critical pore diameter for streaming potential is discussed. 2. The surface charge is calculated for cellulose in contact with solutions of K₃PO₄, K₂CO₃, K₂SO₄, KCl, and ThCl₄. 3. The surface charge of cellulose in contact with a solution of 2 x 10^–4 N NaCl is calculated as a function of temperature and is found to show a sharp break at 39°. This is interpreted in terms of the change of the specific heat of water. 4. A marked ion antagonism is found in NaCl:KCl, KCl:MgCl₂, NaCl:MgCl₂, NaCl:CaCl₂, KCl:CaCl₂, CaCl₂:MgCl₂ mixtures when the surface charge is calculated as a function of concentration.