Subchronic Toxicological Study of Two Artemisinin Derivatives in Dogs

The objective of our study was to profile and compare the systematic changes between orally administered artesunate and intramuscularly injected artemether at a low dose over a 3-month period (92 consecutive days) in dogs. Intramuscular administration of 6 mg kg^-1 artemether induced a decreased red blood cell (RBC) count (anemia), concurrent extramedullary hematopoiesis in the spleen and inhibition of erythropoiesis in the bone marrow. We also observed a prolonged QT interval and neuropathic changes in the central nervous system, which demonstrated the cortex and motor neuron vulnerability, but no behavioral changes. Following treatment with artesunate, we observed a decreased heart rate, which was most likely due to cardiac conduction system damage, as well as a deceased RBC count, extramedullary hematopoiesis in the spleen and inhibition of erythropoiesis in the bone marrow. However, in contrast to treatment with artemether, neurotoxicity was not observed following treatment with artesunate. In addition, ultra-structural examination by transmission electron microscopy showed mitochondrial damage following treatment with artesunate. These findings demonstrated the spectrum of toxic changes that result upon treatment with artesunate and artemether and show that the prolonged administration of low doses of these derivatives result in diverse toxicity profiles.     

5-benzyloxytryptamine: a relatively selective 5-hydroxytryptamine 1D/1B agent.

The ability of nineteen tryptamine derivatives to interact with putative 5-hydroxytryptamine1D (5-HT1D) receptor binding sites in bovine caudate was analyzed. Sixteen of the nineteen agents competed, with variable potency, for these binding sites with Hill slopes of approximately unity. By contrast, 5-carboxyamidotryptamine (5-CT), sumatriptan and 5-benzyloxytryptamine (5-BT) competed with Hill slope values significantly less than unity. These three drugs share, in comparison to the sixteen other tryptamines, relatively large substitutions at the 5-position of the indole moiety. Additional radioligand binding studies with 5-BT indicate that the drug shows relative selectivity for 5-HT1D/1B binding sites. Functionally, 5-BT and sumatriptan inhibit 3H-5-HT release from guinea pig cortical synaptosomes with equal potency but 5-BT is significantly less efficacious than sumatriptan. These data indicate that 5-BT is a relatively selective partial agonist at 5-HT1D receptors.     

Phosphorylation of bovine neurofilament proteins by protein kinase FA (glycogen synthase kinase 3).

A highly purified preparation of protein kinase FA (where FA is the activating factor for phosphatase 1)/glycogen synthase kinase 3 from rabbit muscle readily phosphorylated bovine neurofilaments. All three neurofilament proteins, the high, middle, and low molecular proteins (NF-H, NF-M, and NF-L), were phosphorylated when intact filaments were incubated with the kinase. Experiments with individual proteins showed that NF-M was the best substrate. At protein concentrations of 0.13 mg/ml, the initial rate of NF-M phosphorylation was 30% of that observed for glycogen synthase. Km values were 0.24 mg/ml (7 x 10(-7) M tetramer) for glycogen synthase and 0.10 mg/ml (5 x 10(-7) M dimer) for NF-M. Vmax values were 0.36 mumol/min/mg for glycogen synthase and 0.035 mumol/min/mg for NF-M. Dephosphorylated NF-M was phosphorylated only half as much as native NF-M; this is consistent with the known substrate specificity of the kinase. The possible involvement of FA/GSK-3 in the phosphorylation of neurofilaments in vivo is discussed.     

A phosphoethanolamine-modified glycosyl diradylglycerol in the polar lipids of Clostridium tetani

The polar lipids of the anaerobic bacterium Clostridium tetani, the causative agent of tetanus, have been examined by two-dimensional thin layer chromatography, ESI mass spectrometry, and NMR spectroscopy. Plasmalogen and di- and tetra-acylated species of phosphatidylethanolamine, phosphatidylglycerol, cardiolipin, and N-acetylglucosaminyl diradylglycerol were the major lipids present in most strains examined except for strain ATCC 10779, the parent of strain E88, the first C. tetani strain to have its genome sequenced. This strain contained the same di- and tetra-acylated species but did not contain plasmalogens. All strains contained a novel derivative of N-acetylglucosaminyl diradylglycerol in which a phosphoethanolamine unit is attached to the 6’-position of the sugar, as judged by selective ³¹P-decoupled, ¹H-detected NMR difference spectroscopy. The N-acetylglucosamine (GlcNAc) residue is presumably linked to the 3-positon of the diradylglycerol moiety, and it has the β-anomeric configuration. Very little plasmalogen component was detected by mass spectrometry in the precursors phosphatidic acid and phosphatidylserine, consistent with the idea that plasmalogens are formed from diacylated phospholipids at a late stage of phospholipid assembly in anaerobic clostridia.     

Lymphoid cells recognize an alternatively spliced segment of fibronectin via the integrin receptor alpha 4 beta 1

Using purified recombinant fibronectins we show that WEHI 231 lymphoid cells spread only on fibronectin containing the alternatively spliced V region. Spreading is specifically blocked by peptides from the V25 segment (also called CS-1), which can be selectively spliced out independently of the rest of the V region. Using synthetic peptides we localize the binding site to a 10 amino acid segment that is highly conserved. Integrin alpha 4 beta 1 is a major integrin on the surfaces of these cells and binds specifically to the V25 segment with a primary specificity for the conserved 10 amino acid sequence. Antibodies to integrin alpha 4 inhibit spreading of WEHI 231 cells on V+ fibronectin. Therefore, integrin alpha 4 beta 1 is a fibronectin receptor specific for an alternatively spliced cell adhesion site and may play important roles in selective adhesion of various cell types to specific forms of fibronectin.     

Formation Mechanism and Occurrence Law of Pod Shattering in Soybean: A Review

Seed shattering refers to the phenomenon in which the pods split along the abdominal and back sutures before the crop is received, so that the seeds are spread. Seed shattering is vital to the reproduction of their offspring in wild plants, but it is also the main cause of crop yield loss reason. Pod-explosion resistance is a complex process of physical and physiological and biochemical reactions. Soybean seed shattering phenomenon is widespread, which severely restricts the development of soybean industry. Seed shattering (pod cracking or fruit dropping) is essential for the reproduction of its offspring in wild plants, but it is also the main cause of crop yield loss. This article analyzes the morphology and structure of pods related to seed shattering from the morphology of pods. On the basis of the regularity of the occurrence of seed shattering and the summary of phenotypic index identification methods, physiologically introduced the regulation mechanism of key enzymes and endogenous hormones on seed shattering. The localization, labeling and cloning of seed shattering genes are introduced in molecular biology. The study focused on reviewing the latest advances in the research on soybean seed shattering characteristics, and discussed with the research results of related crops. Finally, the research and application of soybean seed shattering resistance were prospected for several aspects.