Effects of tacrine on deficits in active avoidance performance induced by AF64A in rats

Effects of tacrine (1,2,3,4-tetrahydro-9-aminoacridine) on memory deficits in rats treated with ethylcholine aziridinium ion (AF64A) were studied using active avoidance test in the two-way shuttle box. Neurotoxin AF64A injected at a dose of 6 nmol (icv, bilaterally) causes nonspecific tissue damage in hippocampal fields CA2 and CA3. Two weeks after treatment with 6 nmol, AF64A active avoidance performance of toxin-treated rats was significantly deteriorated compared to vehicle-treated animals estimated in learning test (68±3.5 and 83±3.2% of correct responses, respectively;p<0.01) and in retention test (53±5 and 76±3.6%, respectively;p<0.01). Under these conditions, chronic treatment with tacrine at a daily dose of 1 mg/kg for 12–14 d reverses the effect of AF64A on the active avoidance performance both in learning (78±3.2%) and retention (72±4%) tests. It is supposed that behavioral effects of tacrine considerably depend on a severity of neurodegeneration in the hippocampus.     

Dimebon and Tacrine Inhibit Neurotoxic Action of β-Amyloid in Culture and Block L-type Ca2+ Channels

Dimebon, a Russian-made drug, inhibited toxic effects of beta -amyloid on cultured neurons. Excessive accumulation of beta-amyloid in the brain is characteristic of Alzheimer dementias. Antialzheimer preparations tacrine and dimebon improve survival of cerebellar granule cells during long-term incubation with Ab25-35, the neurotoxic fragment of beta-amyloid. Both preparations can block potential-dependent Ca²⁺ entry into neurons by about 20%, which is explained by their selective action on L-type Ca²⁺ channels. It was assumed that the neuroprotective effect of dimebon and tacrine against Ab25-35 partially depends on inhibition of potential-dependent Ca²⁺ entry.     

Dimebon improves learning in animals with experimental Alzheimer's disease

Systemic administration of antihistamine drug dimebon improves active avoidance conditioning in rats with chronic partial deprivation of cerebral cholinergic functions caused by intracerebroventricular injections of AF64A. The effects of dimebon on learning are similar to those of tacrine used in the treatment of Alzheimer's disease. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 129, No. 6, pp 640–642, June, 2000     

Content of Autoantibodies to Bradykinin and β-Amyloid1-42 as a Criterion for Biochemical Differences between Alzheimer's Dementias

We measured serum content of autoantibodies to -amyloid protein A_1-42, its neurotoxic fragment A_25-35, vasopressin, bradykinin, thrombin, antithrombin III, ₂-macroglobulin, and angiotensin II in patients with various forms of Alzheimer's dementias, including presenile and senile dementias of the Alzheimer type. The ratio of antibradykinin and anti-A_1-42 autoantibody contents differed by 39% in these patients. Our results can be used for the development of a new biochemical method for differential diagnostics of dementias of the Alzheimer type.     

Centromeres and kinetochores of Brassicaceae

The centromere—the primary constriction of monocentric chromosomes—is essential for correct segregation of chromosomes during mitosis and meiosis. Centromeric DNA varies between different organisms in sequence composition and extension. The main components of centromeric and pericentromeric DNA of Brassicaceae species are centromeric satellite repeats. Centromeric DNA initiates assembly of the kinetochore, the large protein complex where the spindle fibers attach during nuclear division to pull sister chromatids apart. Kinetochore assembly is initiated by incorporation of the centromeric histone H3 cenH3 into centromeric nucleosomes. The spindle assembly checkpoint acts during mitosis and meiosis at centromeres and maintains genome stability by preventing chromosome segregation before all kinetochores are correctly attached to microtubules. The function of the spindle assembly checkpoint in plants is still poorly understood. Here, we review recent advances of studies on structure and functional importance of centromeric DNA of Brassicaceae, assembly and function of cenH3 in Arabidopsis thaliana and characterization of core SAC proteins of A. thaliana in comparison with non-plant homologues.     

Chitosan-g-oligo/polylactide copolymer non-woven fibrous mats containing protein: from solid-state synthesis to electrospinning

Graft-copolymers based on bioresorbable synthetic (oligo-/polylactide) and natural (chitosan and collagen/gelatin) components were synthesized through solid-state reactive co-extrusion and used for fabrication of fibrous non-woven mats via the electrospinning technique. The effect of the macromolecular features of the initial components on the copolymer characteristics was evaluated using FTIR-spectroscopy, differential scanning calorimetry and elemental analysis. Dynamic light scattering analysis showed that the copolymers have a tendency to form stable ultra-fine dispersions with a mean size of macromolecular aggregates of 150 nm within chlorinated solvents. The copolymer-containing non-woven fibrous mats were fabricated via an electrospinning procedure using chloroform as a solvent. An effect of the copolymer composition on the casting solution''s viscosity, conductivity and surface tension was evaluated. Scanning electron microscopy showed that the obtained mats consist of randomly distributed fibers with a mean size of ∼5 μm and a more complex morphology than mats fabricated from neat polylactide. The proposed mechanochemical approach to obtain hybrid copolymeric compositions differs from typical liquid-phase methods in terms of high efficiency, simplicity and cleanness.

Amphiphilic chitosan-g-oligo/polylactide graft-copolymers were synthesized through solid-state reactive co-extrusion and used for fabrication of fibrous non-woven mats via the electrospinning technique using chloroform as a solvent.     

Peripheral T-cell lymphoma emerging in a patient with aggressive polymyositis: molecular evidence for neoplastic transformation of an oligoclonal T-cell infiltrate

We report a rare case of peripheral T-cell lymphoma arising in a 52-year-old man with biopsy-proven aggressive polymyositis, who had cardiac involvement, progressive bulbar symptoms, and died 11 months post diagnosis due to multiorgan failure. Using a multimodality approach including immunohistochemistry, genome-wide single nucleotide polymorphism (SNP)-array analysis, and high-throughput sequencing of the complementary determining region 3 (CDR3) of T-cell receptor beta (TCRβ) genes, our study demonstrates a molecular link between polymyositis and T-cell lymphoma, and provides evidence of the rapid and possibly late occurrence of genomic instability during neoplastic transformation of an oligoclonal T-cell population. Immunohistochemical analysis revealed loss of CD5, CD7, and CD8 antigen expression in autopsy tissue samples, as well as the occurrence of aberrant CD56 expression, not seen in pre-mortem biopsies, supporting the emergence of a neoplastic T-cell population. Multiplex polymerase chain reaction and next-generation sequencing of the TCRβ CDR3 region displayed two unique T-cell clones in both the diagnostic biopsy confirming polymyositis and the autopsy muscle tissue exhibiting T-cell lymphoma, linking the two pathological processes. SNP-array analysis revealed complex genomic abnormalities at autopsy but not in the pre-mortem muscle biopsies displaying polymyositis, confirming malignant transformation of the oligoclonal T-cell infiltrate. Our findings raise the possibility that clinically aggressive polymyositis might represent a preneoplastic condition in some instances, similar to certain other autoimmune and inflammatory disorders.     

Glutamate stimulation of acetylcholine release from myenteric plexus is mediated by endogenous nitric oxide

Glutamate was found to be an excitatory neurotransmitter in the enteric nervous system. Although several lines of evidence indicate a role of glutamate in the regulation of gut motility and secretion the physiological significance of glutamatergic transmission is not clear yet. We studied the effect of glutamate on [3H]acetylcholine release and nicotinamide adenine dinucleotide phosphate-diaphorase staining in longitudinal muscle strips with attached myenteric plexus of guinea pig ileum. L-glutamate (100 microM) significantly enhanced both the evoked [3H]acetylcholine release and the optical density of nicotinamide adenine dinucleotide phosphate-diaphorase positive neurones, i.e. the intensity of staining. The non-competitive N-methyl-D-aspartate receptor antagonist MK-801 (3 microM) abolished the stimulatory effect of L-glutamate on acetylcholine efflux. Similarly, the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine (100 microM) significantly reduced the effect of L-glutamate on [3H]acetylcholine release and nicotinamide adenine dinucleotide phosphate-diaphorase staining. Our data suggest that endogenous nitric oxide seems to mediate the stimulatory effect of glutamate on acetylcholine release from guinea pig myenteric neurons.