Immunogenicity of MenACWY-CRM in Korean Military Recruits: Influence of Tetanus-Diphtheria Toxoid Vaccination on the Vaccine Response to MenACWY-CRM

The quadrivalent meningococcal conjugate vaccine (MenACWY-CRM) has been introduced for military recruits in Korea since 2012. This study was performed to evaluate the immunogenicity of MenACWY-CRM in Korean military recruits. In addition, the influence of tetanus-diphtheria toxoids (Td) vaccination on the vaccine response to MenACWY-CRM was analyzed. A total of 75 military recruits were enrolled. Among them, 18 received a dose of MenACWY-CRM only (group 1), and 57 received Td three days before MenACWY-CRM immunization (group 2). The immunogenicity of MenACWY-CRM was compared between the two groups. The serum bactericidal activity with baby rabbit complement was measured before and three weeks after immunization against serogroups A, C, W-135, and Y. The geometric mean titers (GMTs) against four serogroups were significantly increased in both groups after immunization. Compared to group 2, group 1 exhibited significantly higher vaccine responses in several aspects: post-immune GMTs against serogroup A and C, seroresponse rates against serogroup A, and a fold increases of titers against serogroup A, C, and Y. MenACWY-CRM was immunogenic against all vaccine-serogroups in Korean military recruits. Vaccine response to MenACWY-CRM was influenced by Td administered three days earlier.     

A Study on the Effect of Ethanol Extract of Radix Rhapontici on Erythrocyte Immune Function in Rats

This paper mainly studied the effect of ethanol extract of Radix rhapontici on erythrocyte immune function in SD rats with acute blood stasis. The methods used the effect on erythrocyte immune function. After intragastric administration of suspension of ethanol extract of Radix rhapontici to SD rats for 3 weeks, on the 21st day from intragastric administration, SD rats were made into blood stasis model and bloods were collected to determine the C3b, C3bRR, RFIR, and RFER in erythrocyte immune function. Meanwhile, serum total antioxidant activity (TAA), superoxide dismutase (SOD) activity, and serum malondialdehyde (MDA) level of rats were determined, and experimental results were analysed with analysis of variance and Q test. The results showed that the ethanol extract of Radix rhapontici had a very good effect on enhancement of erythrocyte immune function in SD rats.     

The Effects of Plasmodium vivax Gestational Malaria on the Clinical and Immune Status of Pregnant Women in Northwestern Colombia

Objetive:

The study explored the effects of Plasmodium vivax infection on the balance of pro- versus anti- inflammatory cytokines and chemokines and their relationship with some clinical and epidemiology outcomes.

Methods:

Thirty-five pregnant women were recruited. Of these, 15 subjects had malaria at delivery (GM+), and 20 had no exposition to infection throughout the pregnancy (GM-) and at delivery. Epidemiological and clinical data were recorded after reviewing the clinical records. At delivery, whole blood from the mother as well as placental tissue was collected. Diagnosis of infection was performed by thick smear and a polymerase chain reaction (PCR). Expression of pro-inflammatory and anti-inflammatory cytokines and chemokines was measured by a real time PCR.

Results:

The clinical and epidemiological variables explored were similar in both groups, with the exception of gestational age. When comparing the GM+ group with the GM- group, it is clear that although the differences generally are not significant, pro- inflammatory cytokines are elevated in both maternal blood and placental; anti-inflammatory ones are elevated in the mother and reduced in the placenta, and the chemokines are reduced in both compartments, except for MCP-1 which is elevated in all.

Conclusion:

The results appear to be strongly affected by the small number of women with GM by P. vivax at childbirth. Additional studies are needed with larger groups in this and other regions of the country     

Identification of the determinants of tRNA function and susceptibility to rapid tRNA decay by high-throughput in vivo analysis

Sequence variation in tRNA genes influences the structure, modification, and stability of tRNA; affects translation fidelity; impacts the activity of numerous isodecoders in metazoans; and leads to human diseases. To comprehensively define the effects of sequence variation on tRNA function, we developed a high-throughput in vivo screen to quantify the activity of a model tRNA, the nonsense suppressor SUP4_oc of Saccharomyces cerevisiae. Using a highly sensitive fluorescent reporter gene with an ochre mutation, fluorescence-activated cell sorting of a library of SUP4_oc mutant yeast strains, and deep sequencing, we scored 25,491 variants. Unexpectedly, SUP4_oc tolerates numerous sequence variations, accommodates slippage in tertiary and secondary interactions, and exhibits genetic interactions that suggest an alternative functional tRNA conformation. Furthermore, we used this methodology to define tRNA variants subject to rapid tRNA decay (RTD). Even though RTD normally degrades tRNAs with exposed 5′ ends, mutations that sensitize SUP4_oc to RTD were found to be located throughout the sequence, including the anti-codon stem. Thus, the integrity of the entire tRNA molecule is under surveillance by cellular quality control machinery. This approach to assess activity at high throughput is widely applicable to many problems in tRNA biology.     

Influence of the mouse Bcg, Tbc-1 and xid genes on resistance and immune responses to tuberculosis infection and efficacy of bacille Calmette–Guérin (BCG) vaccination

We have studied the role of three mouse distinct non-H-2 genes (BcgTbc-1xid) in several phenomena of antituberculosis immunity and resistance. On the basis of median survival time (MST) of mice following infection with virulent Mycobacterium tuberculosis H37Rv, Bcg gene did not control resistance to the lethal dose of H37Rv infection in non-vaccinated and Myco. bovis (BCG)-vaccinated mice. However, Bcg^r allele, in comparison with Bcg^s allele, determined more effective suppression of an early multiplication in spleens of H37Rv mycobacteria after a low dose (5 × 10⁴ colony-forming units (CFU)) injection. CBA/N mice, which are not protected efficiently against tuberculous challenge by BCG vaccination, were characterized by a decreased in vitro proliferation of immune lymph node cells, both spontaneous and stimulated with mycobacterial antigens. The decreased proliferation was due to immunosuppression caused by interactions between responding T cells and CBA/N antigen-presenting cells (APC). We have confirmed that the defective response to BCG-vaccination in CBA/N mice is linked with the X-chromosome and thus is presumably determined by the xid gene itself. I/St mice (Tbc-1^s), supersusceptible to H37Rv infection, were not able to restrict the growth of H37Rv mycobacteria in spleens, even following infection with a low dose (5 × 10⁴), but restricted the growth of Mycobovis BCG more effectively than Bcg^s mice.     

The Influence of C3435T Polymorphism of the ABCB1 Gene on Genetic Susceptibility to Depression and Treatment Response in Polish Population - Preliminary Report

Background: Despite the high prevalence of depression, the mechanism of the origin of this disease as well as the causes of resistance to therapy in some patients are still not fully understood. Increasingly, the possible role of genetic factors is considered. One of them is polymorphisms in the ABCB1 (MDR1) gene which encodes P-glycoprotein, responsible for the transport of xenobiotics, including antidepressant drugs, through the blood-brain barrier.Methods: C3435T was evaluated in 90 patients with recurrent depressive disorders (rDD). Genotyping was performed using a polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP).Results: The obtained results indicate that the TT genotype occurred more frequently among patients with rDD than in healthy volunteers (p=0.0441). Also, at least one C allele was present significantly less frequent in the study group than in healthy individuals (p=0.0300). The severity of depressive symptoms was higher among patient with the CC genotype in comparison with the other genotypes (p=0.0106) but treatment response to antidepressants was better in this group than among patients with CT or TT genotypes (p=0.0301). Likewise, patients with the T allele have a significantly lower severity of symptoms (p=0.0026) and decreased therapy effectiveness (p=0.0142) than C allele carriers.Conclusions: This study suggests that C3435T polymorphisms in the ABCB1 gene are strongly associated with a predisposition to depression development, the severity of depressive symptoms and the effectiveness of therapy with using different groups of antidepressant agents.     

An experimental model to study the effects of a senna extract on the blood constituent labeling and biodistribution of a radiopharmaceutical in rats

ABSTRACT Cassia angustifolia Vahl (senna) is a natural product that contains sennosides, which are active components that affect the intestinal tract and induce diarrhea. Authors have shown that senna produces DNA (deoxyribonucleic acid) lesions in Escherichia coli cultures and can act as an antifungal agent. Natural drugs can alter the labeling of blood constituents with technetium-99m (^99mTc) and can affect the biodistribution of radiopharmaceuticals. In this work, we have evaluated the influence of a senna extract on the radiolabeling of blood constituents and on the biodistribution of the radiopharmaceutical sodium pertechnetate (Na^99mTcO₄) in Wistar rats. Twelve animals were treated with senna extract for 7 days. Blood samples were withdrawn from the animals and the radiolabeling procedure was carried out. The senna extract did not modify the radiolabeling of the blood constituents. A biodistributional assay was performed by administering Na^99mTcO₄ and determining its activity in different organs and in blood. The senna extract altered the biodistribution of Na^99mTcO₄ in the thyroid, liver, pancreas, lungs and blood. These results are associated with properties of the chemical substances present in the aqueous senna extract. Although these assays were performed in animals, our findings suggest that caution should be exercised when nuclear medicine examinations using Na^99mTcO₄ are conducted in patients who are using senna extract.     

Effects of heme precursors on CYP1A2 and POR expression in the baculovirus/Spodoptera frugiperda system

Objective

CYP1A2 and NADPH-CYP450 oxidoreductase (POR) were expressed in the baculovirus/Spodoptera frugiperda (sf9) system. The aim of this study was to investigate the effects of heme precursors on the expression of CYP1A2 and POR.

Methods

The heme precursors [δ-Aminolaevulinic Acid (5-ALA), Fe³⁺ and hemin] were introduced into the system to evaluate their effects on the expression of CYP1A2, POR and their co-expression. All the proteins were identified using immunoblotting, CO-difference spectroscopy, or cytochrome c assay.

Results

In the present study, functional CYP1A2 and POR were successfully expressed in the baculovirus/sf9 system, and both of them showed high activities. Co-addition of 5-ALA and Fe³⁺ significantly improved expression of CYP1A2 by about 50% compared with the addition of 5-ALA, Fe³⁺ or hemin alone. Either co-addition of 5-ALA and Fe³⁺ or addition of 5-ALA or Fe³⁺ alone improved the POR expression level 2 fold and its activity 7-10 fold compared with control (no addition). However, unlike CYP1A2, there was no difference between the co-addition and addition of these heme precursors alone. Different ratios of BvCYP1A2 to BvPOR also affected the co-expression of CYP1A2 and POR, with a 3:1 ratio of BvCYP1A2 / BvPOR significantly increasing their co-expression. Surprisingly, the addition of 0.1 mM 5-ALA or Fe³⁺ alone, but not their co-addition, could significantly improve the CYP1A2 and POR co-expression (P < 0.05).

Conclusion

5-ALA and Fe³⁺ increased the expression of CYP1A2 and POR in a baculovirus/sf9 system, but the pattern of their expression was different between their expression alone and co-expression.     

Effects of environmental and pharmacological stressors on c-fos and corticotropin-releasing factor mRNA in rat brain: Relationship to the reinstatement of alcohol seeking

We have observed marked heterogeneity among different stressors in their ability to reinstate alcohol seeking in rats. Of the stressors we have tested, only the environmental stressor footshock and the pharmacological stressor yohimbine induce reinstatement. The reasons for such differences among stressors are not known. The purpose of the experiments presented here is to determine the neuroanatomical substrates that underlie these behavioral differences. To this end, we assessed whether stressors effective in inducing reinstatement of alcohol seeking activate a different set of neuronal pathways than do those that are ineffective, using the technique of in situ hybridization of the mRNAs for c-fos, a marker of neuronal activation, and corticotropin-releasing factor (CRF), a stress-related peptide we have shown to be critical to footshock-induced reinstatement of alcohol seeking. Exposure of rats to the environmental stressors footshock, restraint or social defeat, or the pharmacological stressors yohimbine or FG-7142 increased levels of the mRNAs for c-fos and CRF in the brain in a number of areas previously shown to be responsive to stressors. We found regionally specific effects of the stressors on c-fos and CRF mRNA in brain regions associated with the rewarding effects of alcohol and other abused drugs. The two stressors we have previously shown to be effective in inducing reinstatement of alcohol seeking, footshock and yohimbine, induced c-fos mRNA in the shell of the nucleus accumbens, and the basolateral and central amygdalar nuclei. These two stressors also induced CRF mRNA in the dorsal region of the bed nucleus of the stria terminalis. Taken together, these results provide evidence that activity in these regions may be involved in the reinstatement of alcohol seeking induced by these stressors. These results are also in keeping with the previously demonstrated role of CRF neurons in the dorsal bed nucleus of the stria terminalis in the reinstatement of alcohol seeking induced by stress.