Immunomodulating effect of lysozyme in acute cold stress]

It was shown that lysozyme (1 or 5 mg/kg) injection in Wistar rats cooled immersially caused potent immune modulating, antioxidant and hepatoprotector effects. Lysozyme effect was due to heavy erythrocytes and by cytokines induced in spleen (with glass-adhesion at 32-37 degrees C).     

Immunostimulating and protective effects of terrilytin preparations in staphylococcal infection

In mice infected with staphylococci there was observed less pronounced development of the immune response to sheep red blood cells (SRBC) than in intact animals subjected only to immunization. Administration of free terrilytin to the infected mice increased the immune response development induced by SRBC while the use of immobilized terrilytin normalized it. The supernatant liquid of the spleen cells (SLSC) from the mice treated with the free of immobilized terrilytins stimulated development of the immune response to SRBC in the infected animals and inhibited the function of the suppressor cells in the spleen. The immunomodulating and protective effects of the SLSC fractions isolated with column chromatography on Sephadex G-150 were investigated. Substances of the low molecular fraction of the SLSC proteins (molecular weight of 10-15 kD) from the mice treated with the terrilytins showed immunostimulating and protective properties. The factors inducing both the activity types included peptides and the ribonucleotide component playing a significant role in realization of the immunostimulating and protective effects of the free and immobilized proteases.     

Mivazerol, a Novel α2-Agonist and Potential Anti-Ischemic Drug, Inhibits KCl-Stimulated Neurotransmitter Release in Rat Nervous Tissue Preparations

Abstract: In this study, we have investigated the effect of mivazerol, [3-(1H-imidazol-4-yl)methyl-1]-2-hydroxy-benzamide hydrochloride, a new α₂-agonist lacking hypotensive properties and a potential anti-ischemic drug, on the evoked release of norepinephrine, aspartate, and glutamate in tissue preparations from hippocampus, spinal cord T1–T5 section, rostrolateral ventricular medulla, and nucleus tractus solitarii of the brainstem of rat. A simple and efficient in vitro procedure to study pharmacologically the release of norepinephrine and glutamate is described. Tissues were chopped into (0.3 × 0.2 × 0.2 mm³) sections and the resulting minces were used for this study. Exposure to KCl (10–75 mM) for 5 min served as a stimulus for the release response. One, S (for aspartate and for glutamate release), or two such stimuli, S₁ and S₂ (for norepinephrine release) were conducted. The release of norepinephrine (+150% above baseline) was inhibited in a dose-dependent manner by mivazerol in hippocampus (IC₅₀ = 1.5 × 10^?8M), spinal cord (IC₅₀ = 5 × 10^?8M), rostrolateral ventricular medulla (IC₅₀ = 10^?7M), and nucleus tractus solitarii (IC₅₀ = 7.5 × 10^?8M), and by clonidine in hippocampus (IC₅₀ = 5 × 10^?8M), spinal cord (IC₅₀ = 4.5 × 10^?8M), rostrolateral ventricular medulla (IC₅₀ = 2.5 × 10^?7M), and nucleus tractus solitarii (IC₅₀ = 10^?7M). This effect was counteracted by the selective α₂-antagonists yohimbine and rauwolscine. A significant glutamate and aspartate release response was also induced by KCl (35 mmol/L) in hippocampus (+250 and +135%, respectively) and spinal cord (+120 and +55%, respectively), in vitro. However, neither mivazerol nor clonidine, at doses up to 10 µM, had any significant effect on KCl-induced glutamate release in spinal cord, whereas mivazerol blocked completely the release of both amino acids in hippocampus and only the release of aspartate in spinal cord. On the other hand, clonidine (1 µM) was only effective in reducing by 40% the release of aspartate in hippocampus. These data indicate that (1) inhibition of KCl-induced norepinephrine release by mivazerol is mediated by its action on α₂-adrenergic receptors; (2) at concentrations selective for α₂-adrenergic receptors, only mivazerol was effective in blocking the KCl-induced glutamate release in hippocampal tissue; and (3) at the same concentrations, both mivazerol and clonidine were unable to inhibit glutamate release in the spinal cord. These data suggest that prevention of hyperadrenergic activity by mivazerol in perioperative patients may be mediated through its effect on the release of norepinephrine and/or the release of glutamate and aspartate in regions of the CNS that are involved in the control of cardiovascular homeostasis.     

Poly(A)-containing RNA in early embryogenesis of sea urchins

The content, biosynthesis and template activity of poly(A)+ RNA in the early stages of sea urchin development have been studied. The amount of poly(A)+ RNA reaches a maximum at the middle blastula stage in polyribosomes and at the 8-blastomere stage in the cytoplasm. Poly(A)+ RNA synthesis becomes noticeable at the 64-blastomere stage and the spectrum of newly synthesized molecules is different from that at the middle blastula stage. The products of translation in vitro of poly(A)+ RNA at all the stages studied show insignificant differences and contain a major group of polypeptides of molecular mass 10-20 kDa.     

Neuronal responses of the reticular and anterior ventral thalamic nuclei to stimulation of the thalamic ventrolateral nucleus and motor cortex

Responses of 137 neurons of the rostral pole of the reticular and anterior ventral thalamic nuclei to electrical stimulation of the ventrolateral nucleus and motor cortex were studied in 17 cats immobilized with D-tubocurarine. The number of neurons responding antidromically to stimulation of the ventrolateral nucleus was 10.5% of all cells tested (latent period of response 0.7–3.0 msec), whereas to stimulation of the motor cortex it was 11.0% (latent period of response 0.4–4.0 msec). Neurons with a dividing axon, one branch of which terminated in the thalamic ventrolateral nuclei, the other in the motor cortex, were found. Orthodromic excitation was observed in 78.9% of neurons tested during stimulation of the ventrolateral nucleus and in 52.5% of neurons during stimulation of the motor cortex. Altogether 55.6% of cells responded to stimulation of the ventrolateral nucleus with a discharge of 3 to 20 action potentials with a frequency of 130–350 Hz. Similar discharges in response to stimulation of the motor cortex were observed in 30.5% of neurons tested. An inhibitory response was recorded in only 6.8% of cells. Convergence of influences from the thalamic ventrolateral nucleus and motor cortex was observed in 55.7% of neurons. The corticofugal influence of the motor cortex on responses arising in these cells to testing stimulation of the ventrolateral nucleus could be either inhibitory or facilitatory.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 10, No. 5, pp. 460–468, September–October, 1978.     

The role of vascular endothelial growth factor in the regulation of development and functioning of the brain: New target molecules for pharmacotherapy

There is evidence that members of the VEGF family are involved in the crucial processes in the brain: atherosclerosis, cerebral edema, neuroprotection, neurogenesis, angiogenesis, postischemic brain and vessel repair. Most of these effects are mediated by VEGF-A and the VEGFR-2 receptor. VEGF signaling pathways contain some potential targets relevant for pharmacological agents applicable for therapy of neurological diseases affecting the brain.     

The antitumor effect of magnetic nanodisks and DNA aptamer conjugates

Here we describe a method of forming large arrays (up to 10⁹ pieces) of free magnetic Ni-nanodisks 50 nm thick coated on both sides with layers of 5 nm thick Au. The antitumor effect of the magnetic nickel gold-coated nanodisks and DNA aptamer conjugates was evaluated in vivo and in vitro. Under the influence of rotating magnetic field, the studied nanodisks can cause the death of Ehrlich ascites carcinoma cells.     

Association between the ACCN1 gene and multiple sclerosis in Central East Sardinia

Multiple genome screens have been performed to identify regions in linkage or association with Multiple Sclerosis (MS, OMIM 126200), but little overlap has been found among them. This may be, in part, due to a low statistical power to detect small genetic effects and to genetic heterogeneity within and among the studied populations. Motivated by these considerations, we studied a very special population, namely that of Nuoro, Sardinia, Italy. This is an isolated, old, and genetically homogeneous population with high prevalence of MS. Our study sample includes both nuclear families and unrelated cases and controls. A multi-stage study design was adopted. In the first stage, microsatellites were typed in the 17q11.2 region, previously independently found to be in linkage with MS. One significant association was found at microsatellite D17S798. Next, a bioinformatic screening of the region surrounding this marker highlighted an interesting candidate MS susceptibility gene: the Amiloride-sensitive Cation Channel Neuronal 1 (ACCN1) gene. In the second stage of the study, we resequenced the exons and the 3' untranslated (UTR) region of ACCN1, and investigated the MS association of Single Nucleotide Polymorphisms (SNPs) identified in that region. For this purpose, we developed a method of analysis where complete, phase-solved, posterior-weighted haplotype assignments are imputed for each study individual from incomplete, multi-locus, genotyping data. The imputed assignments provide an input to a number of proposed procedures for testing association at a microsatellite level or of a sequence of SNPs. These include a Mantel-Haenszel type test based on expected frequencies of pseudocase/pseudocontrol haplotypes, as well as permutation based tests, including a combination of permutation and weighted logistic regression analysis. Application of these methods allowed us to find a significant association between MS and the SNP rs28936 located in the 3' UTR segment of ACCN1 with p = 0.0004 (p = 0.002, after adjusting for multiple testing). This result is in tune with several recent experimental findings which suggest that ACCN1 may play an important role in the pathogenesis of MS.