Surface Activities of a Lipid Analogue Room-Temperature Ionic Liquid and Its Effects on Phospholipid Membrane.

There are great efforts of synthesizing imidazolium-based ionic liquids (ILs) for developing new antibiotics as these molecules have shown strong antibacterial activities. Compared to a single-hydrocarbon-chained IL, the lipid analogues (LAs) with two chains are more effective. In the present study, the LA molecule MeIm(COOH)Me(Oleylamine)Iodide has been synthesized and its surface activities along with the effectiveness in restructuring of a model cellular membrane have been quantified. The molecule is found to be highly surface active as estimated from the area-pressure isotherm of a monolayer of the molecules formed at the air-water interface. The X-ray reflectivity (XRR) studies of a monolayer dip-coated on a hydrophilic substrate have shown the structural properties of the layer which resembles to those of unsaturated phospholipids. The LA molecules are observed to fluidize a phospholipid bilayer formed by the saturated lipid 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC). At a lower surface pressure, the lipid monolayer of DPPC has exhibited a thickening effect at a low concentration of added LA and a thinning effect at higher concentration. However, at a high surface pressure of the monolayer, the thickness is found to decrease monotonically. The in-plane pressure-dependent interaction of LA molecules with model cellular membrane and the corresponding perturbation in the structure and physical properties of the membrane may be linked to the strong lysing effect of these types of molecules.

Continuous Uptake or Saturation-Investigation of Concentration and Surface-Packing-Specific Hemin Interaction with Lipid Membranes.

Drug design and targeted delivery in cells serve as a flourishing area not only for scientific inquiry, owing to numerous clinical applications, but also for understanding cell interaction with exogenous materials. The membrane localization of heme and its analog hemin, one of the most biologically relevant planar organic molecule, is very important to understand the molecular mechanism of intercalation and adsorption of this cytotoxic molecule after its dissociation from proteins such as hemoglobin. Herein, we investigate the differential behavior of hemin on the soft membrane surfaces of phospholipids by synchrotron-based X-ray scattering techniques, Langmuir monolayer measurements, and molecular dynamics simulation. A continuous hemin uptake from the subphase and intercalation into and/or adsorption on to the membrane surface have been witnessed in a strong membrane surface packing-specific manner. Competitive interactions between hemin-membrane and hemin-hemin are proposed to be responsible for the critical hemin concentration. Up to the limit, a continuous hemin uptake is possible and beyond that the hemin-hemin interaction dominates, effectively reducing the hemin intercalation into the membrane. This structural model of the hemin-uptake process can be generalized to understand the localization and transport across membranes and also for the development and design of new drugs.

Structural changes in cellular membranes induced by ionic liquids: From model to bacterial membranes.

Ionic liquids (ILs) have generated considerable attention recently because of their cytotoxicity and application as antibiotics. However, the mechanism of how they damage cell membranes is not currently well understood. In this paper, the antibacterial activities of two imidazolium-based ILs, namely 1-butyl- 3-methylimidazolium tetrafluroborate ([BMIM][BF4]) and 1-ethyl- 3-methylimidazolium tetrafluroborate ([EMIM][BF4]) have been investigated. The activity of [BMIM][BF4] on gram negative bacteria E. coli is observed to be stronger compared with the short chained [EMIM][BF4]. To explain this observation, the effects of these ILs on the self-assembled structures of model cellular membranes have been investigated. The in-plane elasticity of a monolayer formed at air-water interface by 1,2-dipalmitoyl- sn-glycero- 3-phosphocholine (DPPC) lipids was reduced in the presence of the ILs. The x-ray reflectivity studies on polymer supported lipid bilayer have shown the bilayer to shrink and correspondingly exhibit an increase in electron density. The presence of a certain mol% of negatively charged lipid, 1,2-dipalmitoyl-rac-glycero-3-phospho-L-serine (DPPS), in DPPC mono- and bi-layers enhances the effect considerably.

A High Frequency of HIV-Specific Circulating Follicular Helper T Cells Is Associated with Preserved Memory B Cell Responses in HIV Controllers.

Follicular helper T cells (Tfh) play an essential role in the affinity maturation of the antibody response by providing help to B cells. To determine whether this CD4+ T cell subset may contribute to the spontaneous control of HIV infection, we analyzed the phenotype and function of circulating Tfh (cTfh) in patients from the ANRS CO21 CODEX cohort who naturally controlled HIV-1 replication to undetectable levels and compared them to treated patients with similarly low viral loads. HIV-specific cTfh (Tet+), detected by Gag-major histocompatibility complex class II (MHC-II) tetramer labeling in the CD45RA- CXCR5+ CD4+ T cell population, proved more frequent in the controller group (P = 0.002). The frequency of PD-1 expression in Tet+ cTfh was increased in both groups (median, >75%) compared to total cTfh (<30%), but the intensity of PD-1 expression per cell remained higher in the treated patient group (P = 0.02), pointing to the persistence of abnormal immune activation in treated patients. The function of cTfh, analyzed by the capacity to promote IgG secretion in cocultures with autologous memory B cells, did not show major differences between groups in terms of total IgG production but proved significantly more efficient in the controller group when measuring HIV-specific IgG production. The frequency of Tet+ cTfh correlated with HIV-specific IgG production (R = 0.71 for Gag-specific and R = 0.79 for Env-specific IgG, respectively). Taken together, our findings indicate that key cTfh-B cell interactions are preserved in controlled HIV infection, resulting in potent memory B cell responses that may play an underappreciated role in HIV control.IMPORTANCE The rare patients who spontaneously control HIV replication in the absence of therapy provide a unique model to identify determinants of an effective anti-HIV immune response. HIV controllers show signs of particularly efficient antiviral T cell responses, while their humoral response was until recently considered to play only a minor role in viral control. However, emerging evidence suggests that HIV controllers maintain a significant but "silent" antiviral memory B cell population that can be reactivated upon antigenic stimulation. We report that cTfh help likely contributes to the persistence of controller memory B cell responses, as the frequency of HIV-specific cTfh correlated with the induction of HIV-specific antibodies in functional assays. These findings suggest that T follicular help may contribute to HIV control and highlight the need for inducing such help in HIV vaccine strategies that aim at eliciting persistent B cell responses.

X-ray Reflectivity Study of the Interaction of an Imidazolium-Based Ionic Liquid with a Soft Supported Lipid Membrane.

Ionic liquids (ILs) are important for their antimicrobial activity and are found to be toxic to some microorganisms. To shed light on the mechanism of their activities, the interaction of an imidazolium-based IL 1-butyl-3-methylimidazolium tetrfluoroborate ([BMIM][BF4]) with E. coli bacteria and cell-membrane-mimicking lipid mono- and bilayers has been studied. The survival of the bacteria and corresponding growth inhibition are observed to be functions of the concentration of the IL. The IL alters the pressure-area isotherm of the monolayer formed at an air-water interface by the 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) lipid. The in-plane elasticity of the lipid layer is reduced as a consequence of the insertion of this IL. The X-ray reflectivity study from a polymer-supported lipid bilayer shows strong perturbation in the self-assembled structure of the bilayer due to the interaction. As a consequence, there is a considerable decrease in bilayer thickness and a corresponding increase in electron density. These results, however, depend on the chain configurations of the lipid molecules.

Cytohistological correlation in pituitary tumor and immunological assessment with the help of Ki-67.

BACKGROUND: Tumors of the pituitary gland and sellar region represent approximately 10-15% of all brain tumors. Pituitary adenoma (PA), the most common pathology of the pituitary gland, can be effectively subclassified only with the help of immunohistochemistry (IHC). This is important and needed for individual patient management. AIMS AND OBJECTIVES: The objective of the study was to analyze the importance of intraoperative imprint smear cytology and correlating with final histopathological diagnosis. Furthermore, to classify the different types of PA with the help of IHC, prolactin (PRL), adrenocorticotropic hormone (ACTH), and growth hormone (GH) and to predict the benign, atypical, or malignant nature of the tumor with the help of prognostic marker Ki-67. MATERIALS AND METHODS: A prospective study was done in 34 cases. The patients whose pituitary gland samples are referred from the endocrine and the neurosurgery department to the pathology department for histopathological examinations were selected. We have studied the clinical features, radiology and touch imprint cytology, histopathology, and IHC with the help of PRL, ACTH, GH, and Ki-67 of PA over 2 years. RESULTS: In our study, we had 32 cases of PA of 34 cases over a span of 2 years. We have seen that there is a correlation between cytological and histological diagnosis of the subtypes of PA in 62% cases, and the Kappa statistics show a moderate extent of agreement (Kappa - 0.320, 95% confidence interval = 0.031-0.609). Ki-67 when compared to the radiological grading showed a high degree of comparability (Chi-square test: P < 0.001). All cases with invasion had a higher Ki-67. On using the Fisher's exact test, we found that the Ki-67 expression with GH-producing adenomas and ACTH-producing adenomas was comparable (P = 1.000) while in PRL-producing adenomas too this was not significant (P = 0.269). CONCLUSION: PA can be effectively classified with the help of IHC. Intraoperative cytology is important in diagnosing PA, but histopathology remains the gold standard in diagnosing and differentiating PA from other pathologies of the pituitary gland. The radiological grading together with immunological classification and the prognostic markers of Ki-67 is important in deciding the benign or atypical nature of the adenomas thus helping in better patient management.

Quality of care in patients with diabetic kidney disease in Asia: The Joint Asia Diabetes Evaluation (JADE) Registry.

AIMS: Diabetic kidney disease independently predicts cardiovascular disease and premature death. We examined the burden of chronic kidney disease (CKD, defined as an estimated GFR < 60 ml/min/1.73 m(2) ) and quality of care in a cross-sectional survey of adults (age ≥ 18 years) with Type 2 diabetes across Asia. METHODS: The Joint Asia Diabetes Evaluation programme is a disease-management programme implemented using an electronic portal that systematically captures clinical characteristics of all patients enrolled. Between July 2007 and December 2012, data on 28 110 consecutively enrolled patients (China: 3415, Hong Kong: 15 196, India: 3714, Korea: 1651, Philippines: 3364, Vietnam: 692, Taiwan: 78) were analysed. RESULTS: In this survey, 15.9% of patients had CKD, 25.0% had microalbuminuria and 12.5% had macroalbuminuria. Patients with CKD were less likely to achieve HbA1c < 53 mmol/mol (7.0%) (36.0% vs. 42.3%) and blood pressure < 130/80 mmHg (20.8% vs. 35.3%), and were more likely to have retinopathy (26.2% vs. 8.7%), sensory neuropathy (29.0% vs. 7.7%), cardiovascular disease (26.6% vs. 8.7%) and self-reported hypoglycaemia (18.9% vs. 8.2%). Despite high frequencies of albuminuria (74.8%) and dyslipidaemia (93.0%) among CKD patients, only 49.0% were using renin-angiotensin system inhibitors and 53.6% were on statins. On logistic regression, old age, male gender, tobacco use, long disease duration, high HbA1c , blood pressure and BMI, and low LDL cholesterol were independently associated with CKD (all P < 0.05). CONCLUSIONS: The poor control of risk factors, suboptimal use of organ-protective drugs and high frequencies of hypoglycaemia highlight major treatment gaps in patients with diabetic kidney disease in Asia.

Variation in glass transition temperature of polymer nanocomposite films driven by morphological transitions.

We report the variation of glass transition temperature in supported thin films of polymer nanocomposites, consisting of polymer grafted nanoparticles embedded in a homopolymer matrix. We observe a systematic variation of the estimated glass transition temperature T(g), with the volume fraction of added polymer grafted nanoparticles. We have correlated the observed T(g) variation with the underlying morphological transitions of the nanoparticle dispersion in the films. Our data also suggest the possibility of formation of a low-mobility glass or gel-like layer of nanoparticles at the interface, which could play a significant role in determining T(g) of the films provided.

Effect of Methanolic Leaf Extract of Ocimum basilicum L. on Benzene-Induced Hematotoxicity in Mice.

The aim of the present study was to investigate the protective role of methanolic leaf extract of Ocimum basilicum L. against benzene-induced hematotoxicity in Swiss albino mice. GC analysis and subacute toxicity level of the extract were tested. Mice were randomly divided into three groups among which II and III were exposed to benzene vapour at a dose 300 ppm × 6 hr/day × 5 days/week for 2 weeks and group I was control. Group III of this experiment was treated with the leaf methanolic extract at a dose of 100 mg/kg body weight, a dose in nontoxic range. Hematological parameters (Hb%, RBC and WBC counts), cell cycle regulatory proteins expression and DNA fragmentation analysis of bone marrow cells was performed. There was an upregulation of p53 and p21 and downregulation of levels of CDK2, CDK4, CDK6, and cyclins D1 and E in leaf extract-treated group. DNA was less fragmented in group III compared to group II (P < 0.05). The present study indicates that the secondary metabolites of O. basilicum L. methanolic leaf extract, comprising essential oil monoterpene geraniol and its oxidized form citral as major constituents, have modulatory effect in cell cycle deregulation and hematological abnormalities induced by benzene in mice.

Role of common biochemical markers for the assessment of fracture union.

The progress of fracture union requires close monitoring. Whereas, clinical examination and radiographic studies assess the outcome, biochemical markers like serum alkaline phosphatase and urinary hydroxyproline reflect the actual status of bone resorption and bone formation over a short time frame. 36 patients of long bone fracture were randomly allocated for the study. When the patient reported to the Department of Orthopedics after fracture, serum and urinary samples were collected and X-ray of the affected part were taken. Subsequent samples were collected and X-ray taken just after management (either operative or conservative), after 3rd, 5th, 8th and 12th week, respectively after onset of fracture. According to the course of callus formation the patients were divided into two groups that progressed to proper union or malunion. The levels of serum alkaline phosphatase, urinary total and free hydroxyproline levels were measured and statistically analysed and compared. A statistically significant positive correlation between total urinary hydroxyproline excretion and serum alkaline phosphatase indicate progress towards satisfactory union. Thus, serial monitoring of biochemical markers of bone turnover can be used as an adjunct to clinical and radiological evidence of fracture healing.

Measurement of the interior structure of thin polymer films using grazing incidence diffuse x-ray scattering.

A method is developed for calculating the small-angle x-ray scattering originating from within the interior of a thin film under grazing incidence illumination. This offers the possibility of using x-ray scattering to probe how the structure of polymers is modified by confinement. When the diffuse scattering from a thin film is measured over a range of incident angles, it is possible to separate the contributions to scattering from the interfaces and the contribution from the film interior. Using the distorted-wave Born approximation the structure factor, S(q), of the film interior can then be obtained. We apply this method to analyze density fluctuations from within the interior of a silicon supported molten polystyrene (PS) film. Measurements were made as a function of film thickness ranging from one to ten times the polymer radius of gyration (Rg). The compressibility, calculated by extrapolating the measured S(q) to q=0, agrees well with that of bulk PS for thick films, but thinner films exhibit a peak in S(q) near q=0. This peak, which grows with decreasing thickness, is attributed to a decreased interpenetration of chains and a consequent enhanced compressibility.

Gastric teratoma in a female infant.

Gastric teratoma is a rare lesion seen most often in male infants. This patient, aged one year, female was having a massive benign gastric teratoma. The size of the tumour was 22 cm x 10 cm x 8 cm and weighted 2.250 kg making it one of the largest gastric teratoma. The tumour was removed by surgery. Histopathology revealed presence of all 3 elements in the form of skin, cartilage, fibrofatty tissue, blood vessels and gland with tall columnar epithelium. Postoperative period was uneventful.

Giant congenital infected splenic cyst: An interesting case report and review of the literature.

Splenic cysts are rare lesions. The congenital non-parasitic cysts of the spleen are rarely met in the clinical practice. Primary cysts have a cellular lining that can be caused by congenital events or parasitic infection (Echinococcus). Secondary cysts have no cellular lining and may be of hemorrhagic, serous, inflammatory, or degenerative origin. We report a rare case of congenital cyst of spleen in a child aged 10 years treated successfully by splenectomy because of total involvement of the splenic parenchyma along with involvement of hilum by the cyst, and we review the literature.

Unusual dynamical arrest in polymer grafted nanoparticles.

We present results of temperature dependent measurements of dynamics of polymer grafted nanoparticles with high grafting density with star polymerlike morphology. We observed for the low grafting density and hence low functionality sample, a dynamically arrested state with lowering of temperature, similar to what was conjectured earlier. However the high grafting density sample shows liquidlike relaxation at all measured temperatures. Possible origin of dynamical arrest in the two grafting density sample is discussed.

Complex dynamics in polymer nanocomposites.

Polymer nanocomposites offer the potential to create a new type of hybrid material with unique thermal, optical, or electrical properties. Understanding their structure, phase behavior, and dynamics is crucial for realizing such potentials. In this work we provide an experimental insight into the dynamics of such composites in terms of the temperature, wave vector, and volume fraction of nanoparticles, using multispeckle synchrotron x-ray photon correlation spectroscopy measurements on gold nanoparticles embedded in polymethylmethacrylate. Detailed analysis of the intermediate scattering functions reveals possible existence of an intrinsic length scale for dynamic heterogeneity in polymer nanocomposites similar to that seen in other soft materials like colloidal gels and glasses.

Effect of surfactant-perturbed nanocaging on the ground and excited state proton transfer reaction.

The effect of mixed cyclodextrin-surfactant systems on the ground and excited state proton transfer reactions of 4-methyl-2,6-diformylphenol (MFOH) in aqueous solution has been investigated by steady state and time-resolved fluorescence spectroscopy. It has been found that micellar media perturbs the solvation of MFOH and facilitates nanocaging. In the presence of micelle, MFOH preferentially resides in the interfacial region. Depending on the local pH due to compartmentalization of reaction media, normal or anionic form of MFOH dominates. Encapsulation of the probe within the cyclodextrin nanocavity enhances the shorter lifetime component of MFOH unexpectedly, which has been explained on the basis of reduced solvation and reduced dipolar effect due to confinement.

Thickness induced structural changes in polystyrene films.

Changes to the structure of polystyrene melt films as measured through the spectrum of density fluctuations have been observed as a function of film thickness down to the polymer radius of gyration (Rg). Films thicker than 4Rg show bulklike density fluctuations. Thinner films exhibit a peak in S(q) near q=0 which grows with decreasing thickness. This peak is attributed to a decreased interpenetration of chains resulting in an enhanced compressibility. Measurements were made using small angle x-ray scattering in a standing wave geometry designed to enhance scattering from the interior of the film compared to interface scattering.

Discordance for Ellis-van Creveld syndrome in twins.

Ellis-van Creveld (EVC) syndrome or chondroectodermal dysplasia is a rare autosomal recessive disorder characterised by a variable spectrum of clinical findings. Classical EVC syndrome comprises a tetrad of clinical manifestations of chondrodystrophy, polydactyly, ectodermal dysplasia, and cardiac defects. It is extremely rare for EVC syndrome to occur in one of a pair of newborn twins. Review of the existing literature revealed that only one such case has been reported so far.