In utero sensitization modulates IgG isotype, IFN-γ and IL-10 responses of neonates in bancroftian filariasis.

In utero exposure has been considered as a risk factor for filarial infection. To evaluate the influence of maternal infection on filarial-specific IgG subclass response in neonates and their correlation with plasma levels IL-10 and interferon-γ, 145 pairs of mothers and their respective cord bloods were examined. Transplacental transfer of circulating filarial antigen (CFA) was observed in 34·8% cord bloods from CFA positive mothers. Filarial-specific IgG1, IgG2 and IgG4 responses of cord bloods were found to be positively correlated with CFA of mothers. In contrast, IgG3 responses negatively correlated with CFA of mothers. The % of similarity of recognition pattern in the cord blood with maternal blood was high for IgG3 response than IgG4 in all three groups. An increased levels of IL-10 and decreased levels of interferon gamma (IFN-γ) were observed in cord blood of infected mothers. Interferon gamma was positively correlated with IgG3 and negatively correlated with IgG4 level. On the other hand, IL-10 was positively correlated with IgG4 and CFA, indicating that cytokines may play a role in modulating the immune responses in cord bloods of sensitized foetus. The findings of the study reveal that in utero tolerance or sensitization may influence the filarial-specific immunity to infection in neonates.

Maternal filarial infection: association of anti-sheath antibody responses with plasma levels of IFN-γ and IL-10.

Maternal filarial infection influences the risk of acquiring infection and development of immunity in children. Here we have analysed the blood samples of 60 mothers (24 infected and 36 uninfected) and their corresponding cord bloods to assess the impact of maternal infection on the anti-sheath antibodies and cytokine production in neonates born from them. About 69·4% of non-infected mothers and their cord bloods showed the presence of anti-sheath antibodies, while only 16·6% of the cord bloods from infected mothers were positive for it. The IL-10 level was significantly high in cord bloods of infected mothers compared with non-infected mothers. At the same time the IL-10 level was also observed to be remarkably high in cord bloods of both infected and non-infected mothers negative for anti-sheath antibody. In contrast, IFN-γ levels were significantly high in cord bloods of non-infected mothers compared with infected mothers and the increment was prominent in cord bloods of both infected and non-infected mothers positive for anti-sheath antibody. The study reveals that the presence or absence of anti-sheath antibodies in association with cytokines skews the filarial specific immunity to either Th1 or Th2 responses in neonates. This may affect the natural history of filarial infection in early childhood.

Molecular dynamics simulations of ionic liquid-vapour interfaces: effect of cation symmetry on structure at the interface.

The influence of alkyl chain symmetry of the imidazolium cation on the structure and properties of the ionic liquid-vapour interface has been addressed through molecular dynamics simulations. The anion chosen is bis(trifluoromethylsulfonyl)imide (NTf(2)). Profiles of number densities, orientation of cations, charge density, electrostatic potential, and surface tension have been obtained. At the interface, both cations and anions were present, and the alkyl chains of the former preferred to orient out into the vapour phase. A large fraction of cations preferred to be oriented with their ring-normal parallel to the surface and alkyl chains perpendicular to it. These orientational preferences are reduced in ionic liquids with symmetric cations. Although the charge densities at the interface were largely negative, an additional small positive charge density has been observed for systems with longer alkyl chains. The electrostatic potential difference developed between the liquid and the vapour phases were positive and decreased with increasing length of the alkyl group. The calculated surface tension of the liquids also decreased with increasing alkyl chain length, in agreement with experiment. The surface tension of an ionic liquid with symmetric cation was marginally higher than that of one with an asymmetric, isomeric cation.

Transplacental transfer of filarial antigens from Wuchereria bancrofti-infected mothers to their offspring.

OBJECTIVE: Maternal infection has been considered to be a risk factor for filarial infection in offspring. In order to examine the influence of maternal infection in neonates, we have determined the prevalence of circulating filarial antigen (CFA) and anti-filarial antibodies in 119 maternal and corresponding cord blood samples collected from an area endemic for bancroftian filariasis. METHOD: Prevalence of antigenaemia was detected using Og4C3 circulating filarial antigen enzyme-linked immunosorbent assay. The presence of microfilariae was determined by filtration of a 1 ml sample through a Nuclepore membrane. Antibody isotypes (IgG, IgM, and IgE) to filarial antigen (Setaria digitata antigenic extract) were determined by enzyme linked immunosorbent assay (ELISA). RESULTS: Microfilariae were detected in 14 cases (11.8%), whereas the Og4C3 assay could detect filarial antigen in 44.5% of pregnant mothers. Interestingly, 24.5% of samples born from CFA-positive mothers were found positive for CFA. None of the cord samples from CFA-negative mothers were found positive for CFA. No significant difference was observed in prevalence of filarial-specific IgG, IgM and IgE antibodies in CFA-positive and negative mothers. IgG antibody was detected in 60.5% of maternal and 21.8% of cord samples. IgG antibody in the cord does not differ with the antigen status of the mother. In contrast IgM and IgE antibody prevalence was significantly higher in cord from infected mothers than non-infected mothers (11.3% vs 0 for IgM, 24.5% vs 3.03% for IgE). CONCLUSION: Our study demonstrates the transplacental transfer of circulating filarial antigen from mother to cord. Filaria-specific IgM and IgE antibodies were higher in cord blood from infected mothers than from non-infected mothers. The findings of the study provide additional circumstantial evidence for pre-natal sensitization to filarial antigens developed in utero.

Nanoclusters of room temperature ionic liquids: a molecular dynamics simulation study.

Nanoscopic clusters of the room temperature ionic liquid, 1-n-butyl-3-methylimidazolium hexafluorophosphate ([bmim][PF(6)]) with diameters in the range of 2-8 nm have been studied using equilibrium molecular dynamics simulations. The butyl tail groups of the [bmim](+) ion protrude outwards from the surface of the cluster while the ring centres lie beneath, similar to the situation in a planar ionic liquid-vapour interface. The number densities of cation ring centres show a non uniform distribution near the surface in comparison to that of anions. An electrostatic potential drop of -0.17 V has been calculated across the cluster-vapour interface for the largest cluster studied. The effective interaction potential between the clusters has been evaluated and is found to exhibit a short-ranged, strong attractive well. A linear dependence of this well depth on the cluster size is observed, consistent with the predictions of the interpenetration model for inter-micellar interactions.

Risk factors associated with default among retreatment tuberculosis patients on DOTS in Paschim Medinipur district (West Bengal).

BACKGROUND: In India in 2010, 14.1% of retreatment of TB patients' treatment outcome was 'default'. Since 2002, in Paschim Midnapur District (West Bengal), it has been around 15-20%. OBJECTIVES: To determine the timing, characteristics and risk factors associated with default among retreatment TB patients on DOTS. METHODOLOGY: It was a case control study, conducted in six TB units (TU) of Paschim Midnapur District, which were selected by simple random sampling. Data was collected from treatment records of TUs/DTC. Data was also collected through interviews of the patients using the same pre-tested semi-structured questionnaire from 87 defaulters and 86 consecutively registered non-defaulters registered in first quarter, 2009 to second quarter, 2010. RESULTS: Median duration of treatment taken before default was 121 days (inter-quartile range of 64-176 days). Median number of doses of treatment taken before default was 36 (inter -quartile range of 26-63 doses). No retrieval action was documented in 57.5% cases. Retrieval was done between 0-7 days of missed doses in 29.9% cases. Multiple logistic regression analysis indicated the following important risk factors for default at 95% confidence interval: male-sex limit: [aOR 3.957 (1.162-13.469)], alcoholic inebriation[ aOR6.076 (2.088-17.675)], distance from DOT centre [aOR 4.066 (1.675-9.872)], number of missed doses during treatment [aOR 1.849 (1.282-2.669)] and no initial home visit [aOR 10.607 (2.286 -49.221)]. CONCLUSION: In Paschim Midnapur district, default of retreatment TB occurs mostly after a few doses in continuation phase. Initial home visit, patient provider meeting, retrieval action, community-based treatment as per RNTCP guidelines are required to uplift the programme.

Low frequency vibrational modes of room temperature ionic liquids.

The vibrational spectra of four ionic liquids, sharing the same imidazolium cation but containing different anions-[bmim][NO(3)], [bmim][BF(4)], [bmim][PF(6)], and [bmim][NTf(2)]-have been obtained using normal-mode analysis within the harmonic approximation and from velocity autocorrelation functions from a molecular dynamics trajectory generated using empirical force fields. The vibrational density of states obtained from the two methods agree well. The low frequency modes (<100 cm(-1)) exhibit a red shift with an increase in the anion size. Deuteration of the ring hydrogens leads to a negligible change in this region of the spectrum. The participation ratio of low frequency modes is large, implying that they are not localized to a few atoms. The low frequency band arises primarily from short-range interionic interactions, and the exact peak position is modulated by the cation-anion hydrogen bond strength. Results obtained from these force-field-based calculations are confirmed by ab initio molecular dynamics simulations of crystalline [bmim][PF(6)].