Association of IL‐37 gene polymorphisms with susceptibility to tuberculosis in Saudi subjects

Tuberculosis (TB) is one of the most common infectious diseases worldwide. IL‐37, a novel member of the IL‐1 family, has anti‐inflammatory activity. Various cytokine genes polymorphisms are reportedly associated with susceptibility to TB infection. However, an association between genetic variations in the IL‐37 gene and susceptibility to TB infection has not been investigated. The aim of this case‐control study was therefore to identify such an association in Saudi subjects, in which five single‐nucleotide polymorphisms (SNPs) in the IL‐37 gene were assessed. Serum concentrations of IL‐37 were evaluated using ELISA, and genetic variants genotyped by multiplex PCR and ligase detection reaction. It was found that the C/C genotype of rs2723176 (–6962 A/C) occurs significantly more frequently in patients with active TB and that the C allele of this SNP is associated with TB. In addition, the C allele of rs2723176 SNP was associated with high circulating concentrations of IL‐37. However, the genotype and allele frequency of the other four SNPs (rs3811046, rs3811047, rs2723186 and rs2723187) were not significantly associated with TB infection. In conclusion, the present data suggest that rs2723176 SNP of IL‐37 is involved in the development of TB infection. Furthermore, high circulating concentrations of IL‐37 may have a negative effect on protective immunity against TB infection.     

Presence of a dinucleotide fold in cholera toxin: Possible approach to chemoprophylaxis?

The ADP-ribosyltransferase activity of the A₁. subunit of cholera toxin is specifically inhibited by the dye cibacron blue 3GA. The presence of a ‘dinucleotide fold’ in the A₁ subunit is thus established for the first time. This specific inhibition observed in vitro is successfully exploited in vivo for the inhibition of the diarrheal response brought out by the pure toxin in the rabbit ileal-loop test.     

Isolation and characterisation of a sialic acid-binding lectin (carcinoscorpin) from Indian horseshoe crab Carcinoscorpius rotunda cauda

A sialic acid-binding lectin, carcinoscorpin, has been purified to apparent homogeneity in 40% yield from the Indian horseshoe carb, Carcinoscorpius rotunda cauda. This glycoprotein lectin of molecular weight 420,000 was composed of two non-identical subunits of molecular weights 27,000 and 28,000 as determined by gel electrophoresis in the presence of sodium dodecyl sulfate. The hemagglutination activity of the lectin was susceptible to guanidine-HCl; modification of tyrosyl and tryptophanyl residues also inhibited the activity although alkylation of the -SH group, reduction of disulfide bonds or modification of amino and carboxyl groups were without any effect. The monomeric form of the lectin produced by succinylation of native protein was inactive in binding to sialoglycoconjugates.     

Mechanical variables affecting balloon kyphoplasty outcome--a finite element study

It is still unclear how a vertebral fracture should be stabilised and strengthened without endangering the remaining intact bone of the augmented vertebra or the adjacent vertebrae. Numerical modelling may provide insight. To date, however, few finite element (FE) spine models have been developed which are both multi-segmental and capture a more complete anatomy of the vertebrae. A 3-D, two-functional unit, CT-based, lumbar spine, FE model was developed and used to predict load transfer and likelihood of fracture following balloon kyphoplasty. The fractured anterior wall and injected cement were modelled in a two-functional spinal unit model with osteoporotic bone properties. Parameters investigated included: cement stiffness, cement volume and height restoration. Models were assessed based on stresses and a user-defined fracture-predicting field. Augmentation altered the stress distribution; shielding was dependent on positioning of the cement; and fracture algorithm found incomplete height restoration to increase the likelihood of fracture, particularly in adjacent vertebrae.     

Comparison of Immune Restoration in Early versus Late Alpha Interferon Therapy against Hepatitis C Virus

Early alpha interferon (IFN-α) therapy against hepatitis C virus (HCV) rescues polyfunctional, virus-specific memory CD8⁺ T cells, but whether immune restoration is possible during late therapy remains controversial. We compared immune restoration of HCV-specific memory T cells in patients who cleared HCV infection spontaneously and following early or late IFN therapy. Multifunctional CD4⁺ and CD8⁺ memory T cells were detected in spontaneous resolvers and in individuals treated early following an acute infection. In contrast, limited responses were detected in patients treated during chronic infection, and the phenotype of HCV-specific cells was influenced by autologous viral sequences. Our data suggest that irreversible damage to the HCV-specific memory T-cell response is associated with chronic HCV infection.The majority of acute hepatitis C virus (HCV) infections become chronic, with persistent viremia and serious liver complications (12). Alpha interferon (IFN-α)-based therapy is the only approved treatment for chronic HCV; its success rate ranges from 40 to 90% depending on the infecting genotype (9, 18). The success of therapy is characterized by a sustained virological response (SVR), defined as undetectable HCV RNA in plasma at 6 months after termination of therapy. SVR rates are greatly enhanced if therapy is started between 3 and 6 months following acute HCV infection, but the underlying mechanisms are not well understood (27, 28). We have demonstrated that early interferon therapy for HCV can rescue and select for long-lived polyfunctional CD8⁺ memory T cells (1). Treatment-induced memory T cells were similar in phenotype and function to natural memory T cells generated following spontaneously resolved infection. They expressed high levels of CD127 and Bcl-2 (CD127^hi, Bcl-2^hi) and low levels of PD1 (PD1^lo) and were polyfunctional in nature (1). However, restoration of HCV-specific memory CD4⁺ T cells has not been examined. Furthermore, whether immune restoration is possible following the late initiation of therapy during the chronic phase remains controversial. Kamal et al. demonstrated that SVR is associated with a recovery in HCV-specific CD4⁺ T-cell responses (13). In contrast, Barnes et al. and Rahman et al. demonstrated that the induction of HCV-specific immunity during therapy does not correlate with outcomes (2, 21).     

Cirrhosis pathogenesis: Polymorphism of glutathione S-transferase genes

We tested the association of deletion polymorphism in the GSTT1 and GSTM1 genes for glutathione S-transferases and the A313G single-nucleotide polymorphism in the GSTP1 gene with cirrhosis morbidity and 4-year survival rate among residents of the Tomsk region, West Siberia. The homozygous deletion of the GSTM1 gene (null genotype) proved to be a protective factor against alcoholic and mixed (viral and alcoholic) liver cirrhosis. The frequency of this genotype in patients of the combined group having cirrhosis of any etiology was 39.2%, in patients with alcoholic cirrhosis it was 39.0%, and in patients with mixed cirrhosis it was 34.2%. This genotype was much more frequent among patients of the control group: 64.6%. The GSTM1 null genotype and the GSTP1 A313G polymorphic variant correlated with survival rate. The survivors had a higher GSTM1 null genotype frequency than the dead patients, 46.6 and 30.2%, respectively; a higher frequency of the GSTP1 AA genotype, 63.1 and 40.5%; and a lower frequency of the GSTP1 AG (A313G) genotype (31.1 and 51.2%). The survival rate in patients with the GSTP1 AA genotype was 2.5 times as high as in GG or AG genotype carriers. In patients with the GSTM1 null genotype, the survival rate was twice as high as in patients without the deletion. The 4-year fatal case probability in patients having the heterozygous GSTP1 AG genotype was 2.3 times higher than in patients with the homozygous AA or GG genotypes.     

Development,consumption rates and reproductive biology of <Emphasis Type="Italic">Orius albidipennis</Emphasis> reared on various prey

The predatory bug Orius albidipennis (Reuter) (Hemiptera: Anthocoridae) has tremendous potential as a biological control agent, especially in its native range around the Mediterranean Basin and East Africa. The need to exploit native biological control agents is growing in importance as concerns over the introduction of non-native species continue to increase. However, little is known of the effects of different prey on development and reproduction of O. albidipennis compared with other species of Orius. Therefore, we compared the development, survival, reproductive biology, and prey consumption of O. albidipennis when fed eggs of Ephestia kuehniella Zeller, Tetranychus urticae Koch, and Trialeurodes vaporariorum (Westwood), and larvae of Gynaikothrips ficorum (Marchal), under laboratory of 26 ± 1°C, 60 ± 10% RH and 16L:8D photoperiod. Individuals were reared from the neonate stage until death on one of the four prey types. The type of prey had profound effects on all measured performance traits. The highest survival rate was recorded for nymphs that were fed on E. kuehniella eggs, while the lowest survival rate was observed for those fed on T. vaporariorum eggs. The shortest nymphal period was recorded for nymphs fed on E. kuehniella eggs, while the longest was measured for those fed on T. urticae eggs. During the nymphal period, O. albidipennis consumed significantly more eggs of T. urticae than other prey types, whereas the lowest number of consumed prey were eggs of E. kuehniella. Adult females and males consumed significantly more T. urticae eggs than other types of prey. However, Orius albidipennis females showed the highest fecundity when fed on E. kuehniella eggs, and the lowest when fed on T. vaporariorum eggs. Adult females and males that fed on G. ficorum larvae had significantly longer life spans compared with those fed other prey. Because of their relatively rapid development and high fecundity, O. albidipennis fed E. kuehniella eggs had a significantly higher net reproductive rate (R_o) and intrinsic rate of increase (r _m ) than O. albidipennis fed other prey types. Overall, eggs of E. kuehniella were the most suitable diet for nymphs and adults of O. albidipennis. Although less suitable, O. albidipennis could survive and reproduce on the other prey types, which is a favourable attribute in biological control agents. These results on the effect of different prey types on development and reproduction of O. albidipennis will also contribute to the development of mass rearing programs for biological control agents in developing countries, such as Egypt.     

Stages in development of<Emphasis Type="Italic"> Selaginella diffusa</Emphasis> megaspores

In mature megaspores of Selaginella diffusa (C. Presl) Spring the units of the exospore are ordered and become unordered toward the outer and inner surfaces. The exospore surface is coated with silica at maturity. The insertion of the future gap begins in early stages with formation of many minigaps within the inner part of the exospore distally. The mesospore, like the exospore, is resistant to the acetolysis reaction and can, thus, provisionally be considered to consist of sporopollenin. Unit structures within the outer part of the mesospore are unordered, but become ordered in the middle and inner parts. The inner surface of the mesospore appears verrucate. In maturing megaspores, the mesospore is mostly disintegrated and the inner exospore, which encapsulated the mesospore, remains as a somewhat isolated structure, and is again near the outer exospore. There are connecting strands across the gap between the inner surface of the outer exospore and the surface of the inner exospore. There are also spheres on the outer surface of the inner exospore. Electronic Publication     

Protective effect of arabic gum against cardiotoxicity induced by doxorubicin in mice: a possible mechanism of protection

Arabic gum (AG) is a naturally occurring compound that has been proposed to possess potent antioxidant activity. In this study, the possible effects whereby AG could protect against cardiotoxicity induced by doxorubicin (DOX) in mice were carried out. Administration of single dose of DOX (15 mg/kg, i.p.) induced cardiotoxicity 72 h, manifested biochemically by a significant elevation of serum creatine kinase (CK) (EC 2.7.3.2). In addition, cardiotoxicity was further confirmed by the significant increase in lipid peroxides measured as malondialdehyde (MDA). Administration of AG (25 g/kg) orally for 5 days before and 72 h after DOX injection produced a significant protection against cardiotoxicity induced by DOX. This was evidenced by significant reductions in serum CK and cardiac lipid peroxides. The effect of AG was examined on the superoxide anion radical generated by enzymatic and nonenzymatic methods. The results indicate that AG is a potent superoxide scavenger. The superoxide scavenging effect of AG may explain, at least in part, the protective effect of AG against cardiotoxicity induced by DOX.