Intermembrane transfer and antioxidative action of α-tocopherol in liposomes

Institute of Physiology, Bulgarian Academy of Sciences, Sofia 1113. I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Academy of Sciences of the USSR, Leningrad 194223. University of California, Berkeley 94720. (Presented by Academician of the Academy of Medical Sciences of the USSR S. E. Severin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 109, No. 1, pp. 37–39, January, 1990.     

Maternal and offspring methylenetetrahydrofolate reductase gene C677T polymorphism: does it influence the prevalence of congenital heart defects in Egyptian neonates?

Congenital heart defects (CHDs) are the most prevalent heart diseases in neonates. There is evidence suggesting that the risk of CHDs may be related to the folate status as well as the genetic variants in folate-related genes. Investigating the relationship between methyltetrahydrofolate reductase (MTHFR) C677T gene polymorphism and CHDs in full-term neonates and considering the possible protective role of folate supplementation were made. This study included 26 cases, 18 controls, and their biological mothers. Echocardiography was performed to all neonates for diagnosis of the type of congenital heart disease. Mothers and their off springs were subjected to DNA analysis for MTHFR C677T using polymerase chain reaction restricted fragment length polymorphism. An association between maternal (p?=?0.044) and infant (p?=?0.001) MTHFR C677T polymorphism and transposition of great vessels (d-TGA) was found. Odds ratio (OR) for the genotypes CT and TT versus CC was 10, with 95 % confidence limits (CI) (1.05–95.23) and OR 26 with 95 % CI (2.60–259.29), respectively. Also for the genotypes CT and TT versus CC, an association was found between infant MTHFR C677T polymorphism and atrial septal defect [p?=?0.000; OR 36.4; 95 % CI (3.7–354.40)], ventricular septal defect [p?=?0.025; OR 5.2; 95 % CI (1.2–23.04)], as well as patent ductus arteriosus [p?=?0.000; OR 33.8; 95 % CI (3.5–330.62)]. Maternal folic acid supplementation proved protective against CHDs. MTHFR C677T polymorphism is associated with certain subgroups of CHDs.     

Liraglutide protects against amyloid-β protein-induced impairment of spatial learning and memory in rats

Type 2 diabetes mellitus is a risk factor of Alzheimer's disease (AD), most likely linked to an impairment of insulin signaling in the brain. Liraglutide, a novel long-lasting glucagon-like peptide 1 (GLP-1) analog, facilitates insulin signaling and shows neuroprotective properties. In the present study, we analyzed the effects of liraglutide on the impairment of learning and memory formation induced by amyloid-β protein (Aβ), and the probable underlying electrophysiological and molecular mechanisms. We found that (1) bilateral intrahippocampal injection of Aβ_25–35 resulted in a significant decline of spatial learning and memory of rats in water maze tests, together with a serious depression of in vivo hippocampal late-phase long-term potentiation (L-LTP) in CA1 region of rats; (2) pretreatment with liraglutide effectively and dose-dependently protected against the Aβ_25–35-induced impairment of spatial memory and deficit of L-LTP; (3) liraglutide injection also activated cAMP signal pathway in the brain, with a nearly doubled increase in the cAMP contents compared with control. These results strongly suggest that upregulation of GLP-1 signaling in the brain, such as application of liraglutide, may be a novel and promising strategy to ameliorate the learning and memory impairment seen in AD.     

Evaluation of serum vitamin C, β-carotene and α-tocopherol status in pneumonia of camels

Status of serum vitamin C, β-carotene and α-tocopherol concentrations was evaluated in 17 camels suffering from pneumonia. The grossly affected lungs were collected for histopathological examination from camels at slaughterhouses, and serum samples were processed for measuring β-carotene (micrograms per decilitre), vitamin C (milligrams per decilitre) and α-tocopherol (micrograms per decilitre) levels. Based on histopathological examinations, camels under investigation were classified as acute bronchopneumonia (N?=?3), chronic bronchopneumonia (N?=?4), chronic pleuropneumonia (N?=?3), interstitial pneumonia (N?=?3), embolic pneumonia (N?=?3) and control group (N?=?4). The results revealed significant decreases in serum vitamin C and α-tocopherol concentrations in all investigated types of pneumonia. However, serum β-carotene showed insignificant changes. Results of the present study clearly demonstrated the importance of supplementing camels suffering from pneumonia with sources of vitamins along with the conventional systemic treatment to overcome the oxidative stress and to avoid the possible complications of α-tocopherol and vitamin C deficiencies.     

Age-related changes in expression and activity of DNA polymerase α: some effects of dietary restriction

DNA polymerase α (pol α) purified from human diploid fibroblasts (HDF) and from livers of C57BL/6N mice showed age-related decreases in: (1) mRNA levels; (2) the amount of enzyme isolated per cell; and (3) enzyme activity (HDF); as well as: a) the amount of enzyme isolated; b) the specific activity; and c) the enzyme fidelity (liver). Hepatic pol α from dietary restricted (DR) mice exhibited less of a decline in specific activity and copied synthetic DNA templates with relatively higher fidelity than did enzymes from animals fed ad libitum (AL). Pol α from fetal-derived HDF exhibited increased expression compared with aged donor-derived HDF, with both fetal and old cell pol α in normal cells being expressed at lower levels than in their transformed cell corollaries. Treatment of human pol α from aged donor-derived HDF with a pol α accessory protein isolated from log phase murine cells resulted in increased pol α binding of DNA and increased pol α activity. However, highly active pol α isolated from fetal-derived or transformed HDF, or from transformed murine cells, showed little or no activity enhancement in the presence of accessory protein. These data indicate that, as a function of increased age, there is a decrease in pol α expression and specific activity in HDF, as well as decreases in specific activity and fidelity of pol α in essentially amitotic murine hepatic tissues. Dietary restriction impedes the age-related declines in both activity and fidelity of hepatic pol α in mice. The data further indicate that transformation of slowly dividing HDF is associated with increased expression of pol α, but suggest that increased expression alone is not sufficient to explain the difference in polymerase activity levels between parental and transformed HDF. Lastly, the data suggest that interaction of pol α with an essential accessory protein may be altered as a function of age, an alteration that appears to be correlated with the decline in pol α DNA binding and specific activity.     

“Prepared” fear or socio-cultural learning? Fear conditioned to guns,snakes, and spiders is eliminated by instructed extinction in a within-participant differential fear conditioning paradigm

Across three experiments, we investigated whether electrodermal responses conditioned to ontogenetic fear-relevant (pointed guns) and phylogenetic fear-relevant stimuli (snakes and spiders) would resist instructed extinction in a within-participant differential fear conditioning paradigm. Instructed extinction involves informing participants before extinction that the unconditional stimulus (US) will no longer be presented. This manipulation has been shown to abolish fear conditioned to fear-irrelevant conditional stimuli, but is said to leave fear conditioned to images of snakes and spiders intact. The latter finding, however, has only been demonstrated when fear-relevance is manipulated between-groups. It is also not known whether instructed extinction affects fear conditioned to ontogenetic fear-relevant stimuli, such as pointed guns. In Experiment 1, we demonstrated that fear conditioned to images of pointed guns does not resist instructed extinction. In Experiment 2, we detected some evidence to suggest that fear conditioned to images of snakes and spiders survives instructed extinction but this evidence was not conclusive. In Experiment 3, we directly compared the effects of instructed extinction on fear conditioned to snakes and spiders and to guns and provide strong evidence that fear conditioned to both classes of stimuli is reduced after instructed extinction with no differences between ontogenetic and phylogenetic stimuli. The current results suggest that when fear relevance is manipulated within-participants fear conditioned to both phylogenetic and ontogenetic, fear-relevant stimuli responds to instructed extinction providing evidence in favor of a socio-cultural explanation for “preparedness” effects.     

Effect of ascorbate and α-tocopherol on resistance of β-carotene to oxidation

The efficiency of ascorbate and α-tocopherol as stabilizers of β-carotene, which is widely used in complex therapy and prevention of some diseases accompanied by oxidative stress, was studied. The latency of induced β-carotene oxidation linearly depends on ascorbate concentration, while steady-state rate nonlinearly depends on the concentration of α-tocopherol, which attests to involvement of antioxidants in various stages of chain oxidation of β-carotene. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 130, No. 7, pp. 59–62, July, 2000     

The antioxidant system in combined therapy of epilepsy with traditional anticonvulsants and an antioxidant α-tocopherol

Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 116, N ^o 10, pp. 362–364, October, 1993     

Time course of malonic dialdehyde and α-tocopherol in rat pancreas during the first hours of acute pancreatitis

Time course of malonic dialdehyde and α-tocopherol levels in rat pancreas during the first day of experimental pancreatitis indicates activation of lipid peroxidation and components of the antioxidant system in the involved organ. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 129, No. 5, pp. 536–538, May, 2000     

Development and evaluation of AS03, an Adjuvant System containing α-tocopherol and squalene in an oil-in-water emulsion

AS03 is an Adjuvant System composed of α-tocopherol, squalene and polysorbate 80 in an oil-in-water emulsion. In various nonclinical and clinical studies, high levels of antigen-specific antibodies were obtained after administration of an AS03-adjuvanted vaccine, permitting antigen-sparing strategies. AS03 has been shown to enhance the vaccine antigen-specific adaptive response by activating the innate immune system locally and by increasing antigen uptake and presentation in draining lymph nodes, a process that is modulated by the presence of α-tocopherol in AS03. In nonclinical models of the AS03-adjuvanted prepandemic H5N1 influenza vaccine, increased levels of anti-influenza antibody afforded protection against disease and against virus replication of influenza strains homologous and heterologous to the vaccine strain. By incorporating AS03 in the pandemic H1N1/2009 vaccine, vaccine immunogenicity was increased compared with nonadjuvanted H1N1 vaccines. High H1N1/2009/AS03 vaccine effectiveness was demonstrated in several assessments in multiple populations. Altogether, the nonclinical and clinical data illustrate the ability of AS03 to induce superior adaptive responses against the vaccine antigen, principally in terms of antibody levels and immune memory. In general, these results support the concept of Adjuvant Systems as a plausible approach to develop new effective vaccines.     

What is learned in patterning discriminations? Further tests of configural accounts of associative learning in human electrodermal conditioning

Two Pavlovian SCR conditioning experiments investigated positive and negative patterning discriminations in humans by means of transfer tests. In Experiment 1, positive patterning (A-,B-,AB+) was trained interleaved with non-reinforced presentations of an additional stimulus (C-). Then responding to new compounds consisting of either already trained elements (AC,BC) or new elements (DE) was examined. In Experiment 2, negative patterning (A+,B+,AB-) was trained interleaved with reinforced presentations of an additional stimulus (C+). Again, we examined responding to new compounds consisting of either already trained elements (AC,BC) or new elements (DE). In both experiments the initial patterning discrimination was solved successfully. The response patterns to the test compounds in both experiments were in contradiction to configural accounts of associative learning. In positive patterning human participants seemed to utilize 'number' or some other abstract feature in preference to available concrete stimuli. In negative patterning the abstract dimension of 'separate-versus-together' or 'opposite' was used.     

Does learning style influence academic performance in different forms of assessment?

Educational research on learning styles has been conducted for some time, initially within the field of psychology. Recent research has widened to include more diverse disciplines, with greater emphasis on application. Although there are numerous instruments available to measure several different dimensions of learning style, it is generally accepted that styles differ, although the qualities of more than one style may be inherent in any one learner. But do these learning styles have a direct effect on student performance in examinations, specifically in different forms of assessment? For this study, hypotheses were formulated suggesting that academic performance is influenced by learning style. Using the Honey and Mumford Learning Style Questionnaire, learning styles of a cohort of first year medical and dental students at Queen''s University Belfast were assessed. Pearson correlation was performed between the score for each of the four learning styles and the student examination results in a variety of subject areas (including anatomy) and in different types of assessments – single best answer, short answer questions and Objective Structured Clinical Examinations. In most of the analyses, there was no correlation between learning style and result and in the few cases where the correlations were statistically significant, they generally appeared to be weak. It seems therefore from this study that although the learning styles of students vary, they have little effect on academic performance, including in specific forms of assessment.     

Parents’ experiences of childhood abuse and neglect are differentially associated with behavioral and autonomic responses to their offspring

Although childhood maltreatment has been shown to compromise adaptive parental behavior, little is known what happens in terms of physiological regulation when parents with a history of childhood maltreatment interact with their offspring. Using a sample of 229 parents (131 women), the present study examined whether childhood maltreatment experiences are associated with parents’ behavioral and autonomic responses while resolving conflict with their offspring. Self-reported experienced child maltreatment was measured using a questionnaire assessing abuse and neglect. Parents (M_age = 52.7 years, range_age = 26.6–88.4 years) and their offspring (M_age = 24.6 years, range_age = 7.5–65.6 years) participated in a videotaped parent–offspring conflict interaction task. Parental warmth, negativity, and emotional support were coded. In addition, their pre-ejection period and respiratory sinus arrhythmia were measured as indicators of underlying sympathetic and parasympathetic nervous system reactivity, respectively. Findings demonstrated that experiences of abuse and neglect were associated with behavioral and physiological responses in different ways. Separating these two types of maltreatment in research and in clinical practice might be important.     

Retinoic acid and α-galactosylceramide differentially regulate B cell activation in vitro and augment antibody production in vivo

All-trans-retinoic acid (RA) promotes the maturation and differentiation of B cells, which are known as a type of professional antigen-presenting cells. We show here that CD1d, a major histocompatibility complex class I-like molecule that presents lipid antigens, is expressed in the mouse spleen B cells and is increased by RA. Thus, we hypothesized that RA and the CD1d ligand, α-galactosylceramide (αGalCer), could interact to promote the differentiation, maturation, and antibody response of antigen-activated B cells. In isolated B cells, αGalCer alone markedly stimulated, and RA further increased B cell proliferation, synergizing with the B cell antigen receptor ligation via anti-μ antibody (P < 0.05). The significantly increased cell proliferation stimulated by αGalCer was abrogated in the B cells of CD1d-null mice. RA alone and combined with αGalCer also promoted B cell differentiation by the enrichment of sIgG1-, CD138-, and PNA/Fas-positive B cells (P < 0.05), suggesting a plasmacytic cell differentiation. In vivo, wild-type mice treated with RA and/or αGalCer during primary immunization with tetanus toxoid produced a higher serum anti-tetanus IgG response and had more bone marrow anti-tetanus antibody-secreting cells as determined by enzyme-linked immunospot assay (P < 0.05) in the secondary response, a finding indicative of heightened long-term memory; however, the increased antibody secretion after αGalCer treatment was abolished in CD1d-null mice. We provide evidence here that RA, together with αGalCer, can effectively regulate B cell proliferation and differentiation, ultimately promoting a more efficient antibody response to protein antigen. The results suggest that the combination of RA and αGalCer could be a useful adjuvant combination in vaccine strategies.     

Temporal–spatial expression of ENOLASE after acute spinal cord injury in adult rats

ENOLASE enzymes are abundantly expressed, cytosolic carbon–oxygen lyases known for their role in glucose metabolism. Recent accumulation of evidence revealed that, in addition to its glycolytic function, enolase is also associated with ischemia, hypoxia and to be a neurotrophic factor. To analysis the certain expression and biological function in central nervous system, we performed an acute spinal cord contusion injury model in adult rats. Western blot analysis indicated a marked upregulation of ENOLASE after spinal cord injury (SCI). Immunohistochemistry revealed wide distribution of enolase in spinal cord, including neurons and glial cells. Double immunofluorescent staining for proliferating cell nuclear antigen and phenotype-specific markers showed increases of enolase expression in proliferating microglia and astrocytes. Our data suggest that enolase may be implicated in the proliferation of microglia and astrocytes after SCI.     

Effect of clinical condition and mycophenolate mofetil on plasma retinol, α-tocopherol and β-carotene in renal transplant recipients

Introduction

Plasma antioxidant vitamins (retinol, α-tocopherol, β-carotene) were measured to establish the influence of clinical condition and mycophenolate mofetil (MMF) treatment on the nutritional status of renal transplant recipients.

Material and methods

In 106 adult patients plasma vitamins were measured and 24-h diet history questionnaires were conducted. The MMF influence on plasma vitamins was verified in 61 patients.

Results

The current dietary intakes of vitamins in daily food rations were lower than recommended. Plasma retinol was lower in patients suffering from gastrointestinal disorders (1.25 ±0.48 mg/l vs. 1.55 ±0.70 mg/l) and inversely associated with aminotransferases activity (p = 0.019) and creatinine clearance (p = 0.021). Retinol concentrations were positively associated with plasma creatinine (p = 0.027) and pharmacokinetic parameters of MMF phenyl glucuronide. β-Carotene concentrations were higher in women (0.39 ±0.46 mg/l vs. 0.28 ±0.23 mg/l; p = 0.041) and when MMF was co-administered with cyclosporine vs. tacrolimus (0.45 ±0.62 mg/l vs. 0.25 ±0.19 mg/l). Plasma α-tocopherol correlated negatively with the mycophenolic acid pre-dose concentration (p = 0.027) and was significantly lower in patients treated with calcineurin inhibitors (8.90 ±5.23 mg/l vs. 12.25 ±5.62 mg/l). A positive correlation was observed between α-tocopherol levels and aspartate aminotransferase (p = 0.006). In multivariate regression aspartate aminotransferase and MMF treatment significantly influenced retinol (p < 0.001).

Conclusions

The MMF treatment was associated with significantly lower retinol concentrations. The gastrointestinal disorders occurrence in MMF-treated patients may cause a decrease in retinol absorption. Diet adjustment and/or vitamin A supplementation should be considered.     

Are two threats worse than one? The effects of face race and emotional expression on fear conditioning

Facial cues of racial outgroup or anger mediate fear learning that is resistant to extinction. Whether this resistance is potentiated if fear is conditioned to angry, other race faces has not been established. Two groups of Caucasian participants were conditioned with two happy and two angry face conditional stimuli (CSs). During acquisition, one happy and one angry face were paired with an aversive unconditional stimulus whereas the second happy and angry faces were presented alone. CS face race (Caucasian, African American) was varied between groups. During habituation, electrodermal responses were larger to angry faces regardless of race and declined less to other race faces. Extinction was immediate for Caucasian happy faces, delayed for angry faces regardless of race, and slowest for happy racial outgroup faces. Combining the facial cues of other race and anger does not enhance resistance to extinction of fear.     

Expression patterns of nicotinic subunits α2, α7, α8, and β1 affect the kinetics and pharmacology of ACh-induced currents in adult bee olfactory neuropiles

Acetylcholine (ACh) is the main excitatory neurotransmitter of the insect brain, where nicotinic acetylcholine receptors (nAChRs) mediate fast cholinergic synaptic transmission. In the honeybee Apis mellifera, nAChRs are expressed in diverse structures including the primary olfactory centers of the brain, the antennal lobes (ALs) and the mushroom bodies (MBs), where they participate in olfactory information processing. To understand the nature and properties of the nAChRs involved in these processes, we performed a pharmacological and molecular characterization of nAChRs on cultured Kenyon cells of the MBs, using whole cell patch-clamp recordings combined with single-cell RT-PCR. In all cells, applications of ACh as well as nicotinic agonists such as nicotine and imidacloprid induced inward currents with fast desensitization. These currents were fully blocked by saturating doses of the antagonists α-bungarotoxin (α-BGT), dihydroxy-β-erythroidine (DHE), and methyllycaconitine (MLA) (MLA ≥ α-BGT ≥ DHE). Molecular analysis of ACh-responding cells revealed that of the 11 nicotinic receptor subunits encoded within the honeybee genome, α2, α8, and β1 subunits were expressed in adult Kenyon cells. Comparison with the expression pattern of adult AL cells revealed the supplementary presence of subunit α7, which could be responsible for the kinetic and pharmacological differences observed when comparing ACh-induced currents from AL and Kenyon cells. Together, our data demonstrate the existence of functional nAChRs on adult MB Kenyon cells that differ from nAChRs on AL cells in both their molecular composition and pharmacological properties, suggesting that changing receptor subsets could mediate different processing functions depending on the brain structure within the olfactory pathway.