Effect of classic convulsants on Cl<Superscript>−</Superscript> conductance of the GABA<Subscript>A</Subscript> receptor complex in membranes of cerebral cortex cells at the early stage of kindling

Muscimol-stimulated Cl- conductance of synaptoneurosomes from the cerebral cortex of Wistar rats increased during the early stage of pharmacological kindling not inducing the seizure response in animals. Picrotoxin, bicuculline, and pentylenetetrazole potentiated inhibition of muscimol-dependent 36Cl- entry into synaptoneurosomes, which attested to increased sensitivity of the GABA(A) receptor/Cl- ionophore complex to classic convulsants.     

Role of Intracellular Calcium and Cyclic Nucleotides in Realization of Cardioprotective Effects of δ<Subscript>1</Subscript>- and κ<Subscript>1</Subscript>-Opioid Receptor Agonists

The role of cyclic nucleotides (cAMP, cGMP) and Ca²⁺-ATPase of the sarcoplasmic reticulum in the mechanism of cardioprotective effects of selective δ₁- and κ₁-opioid receptor agonists DPDPE and U-50488 was studied under conditions of global ischemia and reperfusion of isolated and perfused rat heart. Activation of both types of opioid receptors 2-fold reduced the reperfusion release of creatine phosphokinase. The cardioprotective effect of U-50488 was paralleled by a 2-fold decrease in cAMP content in the myocardium, while DPDPE did not modify the content of cAMP throughout the experiment. None of these substances changed the content of cGMP in the myocardium. The cardioprotective effect of DPDPE was not observed after inhibition of sarcoplasmic reticulum Ca²⁺-ATPase with cyclopiazonic acid. The cardioprotective effect of U-50488 was associated with reduction of cAMP level in the myocardium, while the cytoprotective effect of DPDPE was mediated by opioidergic modulation of Ca²⁺ transport at the level of the sarcoplasmic reticulum.     

Cl<Superscript>−</Superscript> conduction of GABA<Subscript>A</Subscript> receptor complex of synaptic membranes in the cortex of rats at the middle stage of chronic cerebral epileptization (pharmacological kindling)

Experiments on Wistar rats showed a decrease in basal and muscimol-stimulated ³⁶Cl⁻ entry into synaptoneurosomes isolated from the cerebral cortex during the middle stage of kindling (30 mg/kg pentylenetetrazole intraperitoneally for 14 days) characterized by the development of convulsions of higher (2 points) severity in comparison with the previous stage. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 144, No. 11, pp. 507–509, November, 2007     

Identification of two ß-tubulin isotypes of <Emphasis Type="Italic">Clonorchis sinensis</Emphasis>

The ß-tubulin coding sequences were investigated for the Chinese liver fluke, Clonorchis sinensis. A cDNA library of adult C. sinensis was screened with cDNA probes synthesized by polymerase chain reaction using degenerate primers, and two ß-tubulin cDNAs, CsTB1 and CsTB3, were subsequently cloned. The CsTB1 and CsTB3 cDNA were 2,082 and 1,486 bp long and encoded 445 and 444 amino acids, respectively. The two clones were identical 78% in their coding sequences and 97% in deduced sequences. Moreover, the CsTB1 had 3′-UTR 592 bp longer than that of CsTB3. The CsTB1 and CsTB3 polypeptides were highly homologous (88–99%) with those of known ß-tubulins of other helminthes with a variation at the C-terminal region. In CsTB1 and CsTB3 polypeptides, two amino acids Tyr 200 and Phe 167 were conserved. The phylogenetic analysis of selected sequences indicates that the ß-tubulins can be organized into five groups and that the two ß-tubulin isotypes of C. sinensis are contained within one group with those of other trematodes and vertebrates.     

Interaction of Afobazole with σ<Subscript>1</Subscript>-Receptors

The capacity of living systems to perceive low-intensity stimuli sometimes inducing protective reactions is still little studied. Incubation of neurons under conditions increasing the content of cAMP and Ca²⁺ increases the amplitude of their responses to lidocaine (10⁻³ M). After cell preconditioning with low concentrations of lidocaine (10⁻¹⁵ M) under these conditions, the protective effects of “ineffective” concentrations were detected, because the response amplitude did not decrease. It was hypothesized that the basic amplitude responses retrieved by lidocaine in a concentration of 10⁻³ M are memory traces about the effects of this compound in subthreshold concentrations. Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 147, No. 1, pp. 43-46, January, 2009     

Effect of interleukin-1β on NMDA-induced <Superscript>45</Superscript>Ca<Superscript>2+</Superscript> uptake by synaptosomes of rat brain cortex

The effect of interleukin-1β on presynaptic NMDA receptors was evaluated by studying NMDA-induced ⁴⁵Ca²⁺ uptake by synaptosomes from rat brain cortex. Interleukin-1β inhibited ⁴⁵Ca²⁺ uptake by synaptosomes. Our results indicate that interleukin-1β modulates presynaptic NMDA receptors and is probably involved in the regulation of synaptic transmission in the central nervous system. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 140, No. 12, pp. 645–646, December, 2005     

Comparative study of analgesic potency of ACTH<Subscript>4–10</Subscript> fragment and its analog semax

The effects of ACTH_4–10 fragment and its analog semax on nociception were examined on various animal models. ACTH_4–10 in a dose of 0.5 mg/kg decreased nociception in rats during hindpaw compression test and in mice subjected to acetic acid writhing test. Lower doses of ACTH_4–10 produced no analgesic effect. Semax (0.015–0.500 mg/kg) decreased pain sensitivity in all experimental models. Hence, the substitution of three C-terminal amino acid residues in ACTH_4–10 for Pro-Gly-Pro sequence augmented the analgesic potency of the peptide after its peripheral injection. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 143, No. 1, pp. 8–12, January, 2007     

Decreased postural adaptation in patients with phobic postural vertigo—An effect of an “anxious” control of posture?

Postural adaptability and responses elicited by vibratory stimulation to the calf muscles recorded on a force platform with eyes open or closed were analyzed in 39 patients suffering from Postural Phobic Vertigo (PPV) (17 men and 22 women, mean age 49 years) and 24 healthy subjects (14 men, 10 women, mean age 38 years). The vibration induced increased body sway in both groups, but the adaptation pattern differed significantly. With eyes open the PPV patients decreased their induced body sway over time (−32%, p < 0.01), which the controls did not. With eyes closed the PPV patients reduced their induced body sway over time to a much lesser extent than the controls (PPV: −28%, p < 0.05, controls: −57%, p < 0.001). These new findings show that PPV patients adapt to proprioceptive perturbation to a lesser extent than normal subjects and that PPV patients do not use visual information as efficiently to modulate postural control. The results support the hypothesis that a cognitive set of posture, an “anxious control”, may underlie the symptoms of PPV, i.e. an increased readiness to react to any perturbation or deviation.     

‘Down-shifting’ among top UK scientists? – The decline of ‘revolutionary science’ and the rise of ‘normal science’ in the UK compared with the USA

It is sometimes asserted that UK science is thriving, at other times that it has declined. We suggest that both assertions are partly true because the UK is thriving with respect to the volume of 'normal' science production but at the same time declining in the highest level of 'revolutionary' science. Revolutionary science may be distinguished from normal science in that revolutionary science aims at generating qualitative advances which change the direction of established science, while 'normal' science aims at incremental progress extrapolating from established science. Revolutionary science has been measured by counting national numbers of science Nobel laureates and ISI Highly Cited (HiCi) scientists; normal science has been measured using the total volume of scientific publications and citations at both national and institutional levels. By these criteria the UK has been progressively catching-up with the USA in terms of normal science since the 1990s. At the same time the UK has declined in revolutionary science over recent decades by a significant brain drain of future Nobel laureates and HiCi scientists, and a sharply reduced success (both in absolute and compared with the USA) at winning science Nobel prizes. One possible cause for this pattern could be a time-lag, such that the UK's improved science production since about 1990 may eventually work-through into improved UK performance in revolutionary science. More pessimistically, this pattern may reflect a strategic down-shift of the best UK-resident scientists away from revolutionary science and towards less-ambitious and safer normal science which is more productive in the short term.     

A Singular Role of I<Subscript>K1</Subscript> Promoting the Development of Cardiac Automaticity during Cardiomyocyte Differentiation by I<Subscript>K1</Subscript><Emphasis Type="Bold">–</Emphasis>Induced Activation of Pacemaker Current

The inward rectifier potassium current (I_K1) is generally thought to suppress cardiac automaticity by hyperpolarizing membrane potential (MP). We recently observed that I_K1 could promote the spontaneously-firing automaticity induced by upregulation of pacemaker funny current (I_f) in adult ventricular cardiomyocytes (CMs). However, the intriguing ability of I_K1 to activate I_f and thereby promote automaticity has not been explored. In this study, we combined mathematical and experimental assays and found that only I_K1 and I_f, at a proper-ratio of densities, were sufficient to generate rhythmic MP-oscillations even in unexcitable cells (i.e. HEK293T cells and undifferentiated mouse embryonic stem cells [ESCs]). We termed this effect I_K1-induced I_f activation. Consistent with previous findings, our electrophysiological recordings observed that around 50% of mouse (m) and human (h) ESC-differentiated CMs could spontaneously fire action potentials (APs). We found that spontaneously-firing ESC-CMs displayed more hyperpolarized maximum diastolic potential and more outward I_K1 current than quiescent-yet-excitable m/hESC-CMs. Rather than classical depolarization pacing, quiescent mESC-CMs were able to fire APs spontaneously with an electrode-injected small outward-current that hyperpolarizes MP. The automaticity to spontaneously fire APs was also promoted in quiescent hESC-CMs by an I_K1-specific agonist zacopride. In addition, we found that the number of spontaneously-firing m/hESC-CMs was significantly decreased when I_f was acutely upregulated by Ad-CGI-HCN infection. Our study reveals a novel role of I_K1 promoting the development of cardiac automaticity in m/hESC-CMs through a mechanism of I_K1-induced I_f activation and demonstrates a synergistic interaction between I_K1 and I_f that regulates cardiac automaticity.     

Effects of Hydroxyapatite and Biostite<Superscript>®</Superscript> on Osteogenic Induction of hMSC

When isolated from the iliac crest human mesenchymal stem cells (hMSC) differentiate into osteoblast-like cells with appropriate stimulation in culture. This in vitro study tested the hypothesis that Biostite^® and hydroxyapatite (HA) affect proliferation and differentiation of hMSC into osteoblastic cells. Cell proliferation was determined by measuring ³H-thymidine incorporation into DNA and typical markers of osteoblastic phenotype were determined by RT-PCR assay. No differences emerged in cell proliferation cultures with Biostite^® or hydroxyapatite (HA), but gene expression analysis revealed higher expression of collagen, alkaline phosphatase (ALP), osteopontin and bone sialoprotein (BSP) in the presence of Biostite^®. TGFβ₂ production, as assessed by an Elisa kit, and Runx2 expression by RT-PCR, were greater in Biostite cultures, suggesting Biostite^® provides a better environment for hMSC differentiation into osteoblasts and is, potentially, a more promising bone-filling material than HA.     

Histochemical study of mast cells from the thymus of mice receiving ACTH<Subscript>1–24</Subscript>

Synthetic ACTH_1–24 analogue administered in a daily dose of 0.01 mg/kg decreased the number and size of mast cells and increased intracellular serotonin concentration. ACTH_1–24 induced degranulation of young mast cells and release of undersulfated heparin. Correlation analysis showed that hormonal imbalance produced by ACTH_1–24 was accompanied by redistribution of bioamines. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 138, No. 7, pp. 107–110, July, 2004     

Genetic basis of the <Emphasis Type="Italic">ovc</Emphasis> phenotype of <Emphasis Type="Italic">Neurospora:</Emphasis> identification and analysis of a 77 kb deletion

The ovc mutant of Neurospora crassa accumulates more carotenoids than the wild type in the light, is sensitive to high osmotic pressure and exhibits an altered aerial development. The three traits are complemented by a single gene, cut-1, but only the two latter are exhibited by a mutant of this gene carrying a premature stop mutation. Targeted cut-1 deletion results in a normal carotenoid content, confirming the involvement of at least a second gene in the carotenoid-overproducing phenotype of the ovc strain. Molecular analysis of ovc genomic DNA indicates the absence of a large DNA segment affecting the gene cut-1. A PCR walking approach allowed the identification of a deletion extending along 77,078 bp on linkage group IV. The break-points are located in ApA/TpT sequences, suggesting the involvement of UV-induced thymine dimers in the origin of the deletion. The ovc mutant lacks 21 predicted ORFs, including cut-1 as the only known genetic marker, and four ORFs from a 22-member transmethylase gene family. Ten ORFs have no similarity with any predicted gene from other species. Three of them are closely related by sequence and linkage, evoking ancestral gene duplications.Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users.     

Cardioprotective effect of κ<Subscript>1</Subscript>-opioid receptor activation and role of cAMP in its realization

The cardioprotective and antiarrhythmic effects of a selective κ₁-opioid receptor agonist U-50,488 were studied during experimental 45-min total ischemia and 30-min reperfusion of isolated rat heart. The opioid had no effect on the incidence and type of reperfusion arrhythmias. U-50,488 in a concentration of 0.1 μM inhibited reperfusion-induced release of creatine phosphokinase and decreased cAMP concentration in the myocardium by 2 times. These parameters remained unchanged after treatment with U-50,488 in a concentration of 1 μM. The cardioprotective effect of U-50,488 was probably associated with a decrease in cAMP concentration in heart cells. U-50,488 in a concentration of 1 μM produced no cardioprotective effect, which can be explained by its interaction with an unknown non-opioid receptor in cardiomyocytes. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 143, No. 1, pp. 28–31, January, 2007     

Tracing the origins of “fetal origins” of adult diseases: Programming by oxidative stress?

Too small size at birth (due to poor fetal growth and/or preterm delivery) has been associated with substantially elevated risks of the metabolic syndrome (dislipidemia, insulin resistance, hypertension), type 2 diabetes and cardiovascular disease in adulthood. The mechanisms of such "fetal origins" or "programming" of disease phenomenon remain unresolved. Too large size at birth seems also associated with an increased risk. Many known or suspected causes of or conditions associated with adverse (poor or excessive) fetal growth or preterm birth have been associated with oxidative stress. Plausibly, oxidative stress may be a common link underlying the superficial "programming" associations between adverse fetal growth or preterm birth and elevated risks of certain chronic diseases. The mechanisms of oxidative stress programming may be through directly modulating gene expression or indirectly through the effects of certain oxidized molecules. Experimental investigations have well demonstrated the role of redox balance in modulating gene expression, and recent studies indicate that both the insulin functional axis and blood pressure could be sensitive targets to oxidative stress programming. Adverse programming may occur without affecting fetal growth, but more frequently among low birth weight infants merely because they more frequently experienced known or unknown conditions with oxidative insults. As oxidative stress levels are easily modifiable during pregnancy and early postnatal periods (which are plausible critical windows), the hypothesis, if proved valid, will suggest new measures that could be very helpful on fighting the increasing epidemic of the metabolic syndrome, type 2 diabetes and cardiovascular disease. Currently, there are several ongoing large randomized trials of antioxidant supplementation to counter oxidative stress during pregnancy for the prevention of preeclampsia. It would be invaluable if long-term follow-ups of infants born to women in such trials could be realized to test the oxidative stress programming hypothesis in such experimental trial settings.     

Effect of IFN-α on CC1<Subscript>4</Subscript>-Induced Fibrosis of the Liver and Immune Status in Mice of Different Age

In young, adult, and old mice fibrosis was induced by administration of CC1₄ and treated with IFN-α. Liver fibrosis was evaluated by morphometry of argyrophilic fibers, immune status by the splenocyte proliferative response. Minimum immunosuppression and maximum antifibrotic effect were observed in young mice, while adult mice exhibited pronounced immunotoxicity and weak response to interferon therapy.__________Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 139, No. 3, pp. 303–306, March, 2005