High-throughput screening and quantitative structure-efficacy relationship models of potential displacer molecules for ion-exchange systems

The stability and structure of protein-containing water-in-oil (w/o) microemulsions were investigated by using the large protein immunoglobulin G (IgG, MW 155,000) in a mixture comprised of brine, sulfosuccinic acid bis [2-ethylhexyl]ester (sodium salt), and isooctane. We explored factors affecting the initial uptake of IgG into the w/o microemulsion and its subsequent release to a solid (precipitate) phase, and the kinetics of the latter process. Influences of such parameters as pH, ionic strength, and protein concentration on the solubilization and precipitation of bovine IgG in the organic phase are described. The structure and dynamics in microemulsions containing bovine IgG were probed by using dynamic light scattering, and it was found that the presence of IgG in the microemulsion induced strong attractive forces between the droplets. Based on results obtained by using these various experimental approaches, a model for protein solubilization and release is proposed. In this model, we propose the formation of clusters within which bovine IgG resides and which substantially slow the kinetics of protein release from the droplets to the precipitate phase.     

Sandwich microgravimetric immunoassay: sensitive and specific detection of low molecular weight analytes using piezoelectric quartz crystal

A multi-channel sandwich microgravimetric immunoassay (sMIA), using the quartz crystal microbalance (QCM) principle, has been developed to quantify low molecular weight substances in standard solutions. An antigen is sandwiched between two antigen-specific antibodies: the first antibody is coated on the quartz crystal surface and the second antibody is used for the detection of analyte. The concentration of low molecular weight antigen (insulin was used in this study, M _r6000 Da) was correlated with the shift of resonant frequency of QCM system before and after second antibody binding to insulin. The developed assay is highly specific showing low cross-reactivity, and is sensitive to approx. 1 ng insulin ml^–1 with a linear response for insulin from 10 g ml^–1 to 10 ng ml^–1 in standard solutions. The technique may also be applied for the detection of other small biomolecules.     

Bacterial glycoproteins: functions,biosynthesis and applications

Although widely distributed in eukaryotic cells glycoproteins appear to be rare in prokaryotic organisms. The prevalence of the misconception that bacteria do not glycosylate their proteins has been a subject matter of discussion for a long time. Glycoconjugates that are linked to proteins or peptides, generated by the ribosomal translational mechanism have been reported only in the last two to three decades in a few prokaryotic organisms. Most studied prokaryotic glycoproteins are the S-layer glycoproteins of Archeabacteria. Apart from these, membrane-associated, surface-associated, secreted glycoproteins and exoenzymes glycoproteins are also well documented in both, Archea and Eubacteria. From the recent literature, it is now clear that prokaryotes are capable of glycosylating proteins. In general, prokaryotes are deprived of the cellular organelles required for glycosylation. In prokaryotes many different glycoprotein structures have been observed that display much more variation than that observed in eukaryotes. Besides following similar mechanisms in the process of glycosylation, prokaryotes have also been shown to use mechanisms that are different from those found in eukaryotes. The knowledge pertaining to the functional aspects of prokaryotic glycoproteins is rather scarce. This review summarizes developments and understanding relating to characteristics, synthesis, and functions of prokaryotic glycoproteins. An extensive summary of glycosylation that has been reported to occur in bacteria has also been tabulated. Various possible applications of these diverse biomolecules in biotechnology, vaccine development, pharmaceutics and diagnostics are also touched upon.     

Unusual presentation of choriocarcinoma

Background  

Choriocarcinoma is an aggressive neoplasm arising in the body of the uterus. The disease normally spreads to lung and brain.     

Central Mucoepidermoid carcinoma of mandible – A case report and review of the literature

BACKGROUND: Primary central mucoepidermoid carcinoma of jaws is a rare lesion comprising 2-3% of all mucoepidermoid carcinomas reported in literature. CASE PRESENTATION: The case presented here illustrates the hypothesis that its specific pathogenesis is unknown. CONCLUSIONS: Mucoepidermoid carcinoma of the jaw is a rare tumour of unknown aetiology. Although about a 100 cases has been reported in literature, the speculation on its aetiopathogenesis has mainly centred on the pluripotential capabilities of the epithelial lining of odontogenic cysts.     

Phenotypic variation of Plasmodium falciparum merozoite proteins directs receptor targeting for invasion of human erythrocytes

The members of the phylum Apicomplexa parasitize a wide range of eukaryotic host cells. Plasmodium falciparum, responsible for the most virulent form of malaria, invades human erythrocytes using several specific and high affinity ligand-receptor interactions that define invasion pathways. We find that members of the P. falciparum reticulocyte-binding homolog protein family, PfRh2a and PfRh2b, are expressed variantly in different lines. Targeted gene disruption shows that PfRh2b mediates a novel invasion pathway and that it functions independently of other related proteins. Phenotypic variation of the PfRh protein family allows P. falciparum to exploit different patterns of receptors on the erythrocyte surface and thereby respond to polymorphisms in erythrocyte receptors and to evade the host immune system.     

A Molecular Electrostatic Potential Mapping Study of Some Fluoroquinolone Anti-Bacterial Agents

Molecular electrostatic potential (MEP) maps of some fluoroquinolones having varying degrees of activity against the bacterium Staphylococcus Aureus have been studied using the optimized hybridization displacement charges (HDC) combined with Löwdin charges obtained by the AM1 method. The roles of different substitutions at the N₁-position in the parent quinolone ring have been studied. The conformation of the carboxylic group attached to the quinolone ring was shown to be such that there is an intramolecular hydrogen bonding between the hydrogen atom of this group and the oxygen atom of the carbonyl group of the quinolone moiety. The carbonyl oxygen atom of the quinolone moiety, hydroxyl oxygen atom of the carboxylic group and the terminal nitrogen atom of the piperazin ring attached to the quinolone ring appear to be involved in the action of the drugs through electrostatic interactions while the N₁-alkyl substituents seem to be involved in the same through hydrophobic interactions.     

Mutagenic analysis of putative domain II and surface residues in mosquitocidal Bacillus thuringiensis Cry19Aa toxin

The growing resistance against antibiotics demands the search for alternative treatment strategies. Photodynamic therapy is a promising candidate. The natural intermediate of chlorophyll biosynthesis, protochlorophyllide, was produced, purified and tested as a novel photosensitizer for the inactivation of five model organisms including Staphylococcus aureus, Listeria monocytogenes and Yersinia pseudotuberculosis , all responsible for serious clinical infections. When microorganisms were exposed to white light from a tungsten filament lamp (0.1 mW cm⁻²), Gram-positive S. aureus, L. monocytogenes and Bacillus subtilis were photochemically inactivated at concentrations of 0.5 mg L⁻¹ protochlorophyllide. Transmission electron microscopy revealed a disordered septum formation during cell division and the partial loss of the cytoplasmic cell contents. Gram-negative Y. pseudotuberculosis and Escherichia coli were found to be insensitive to protochlorophyllide treatment due to the permeability barrier of the outer membrane. However, the two bacteria were rendered susceptible to eradication by protochlorophyllide (10 mg L⁻¹) upon addition of polymyxin B nonapeptide at 50 and 20 mg L⁻¹, respectively. The release of DNA and a detrimental rearrangement of the cytoplasm were observed.     

Video Capsule Endoscopy in Patients with Chronic Abdominal Pain with or without Associated Symptoms: A Retrospective Study

Background

Chronic abdominal pain (CAP) is a common indication for gastroenterology referrals. More insidious causes of CAP isolated to the small bowel, such as malignancies and Crohn’s disease, are rising in incidence and causing more gastroenterologists to evaluate their patients with video capsule endoscopy (VCE). However, the role of VCE in patients with CAP is still unclear.

Aims

We assessed the efficacy of VCE in patients with CAP and whether it led to findings that contributed to disease management and meaningful interventions.

Methods

This retrospective study evaluated 607 capsule endoscopy studies at an open referral endoscopy unit. Ninety of the studies were for CAP. These studies were compared to those performed for other indications to compare diagnostic yield. In addition, we investigated whether VCE led to an intervention that improved clinical outcomes.

Results

Overall, the number of abnormal findings in CAP patients was significantly lower than VCE performed for other indications (24.4% vs 39.0%, respectively p = 0.009). When patients with CAP presented with other pertinent clinical findings (e.g. nausea, weight loss, anemia, history of in inflammatory bowel disease, etc.), the likelihood of an abnormal finding increased to a level that was not different from those who received VCE for other indications (27.1%, p = 0.10). The findings from VCE lead to changed management and improved outcomes in 16.2% of CAP patients with associated symptoms. However, the subgroup that benefited the most were those who had a prior history of Crohn’s disease. Patients with CAP who did not have any associated symptoms continued to have a significantly lower abnormal finding rate compared to those who received VCE for other indications (19.4%, p = 0.03) and VCE rarely led to a change in management that would improve outcomes (5.6%).

Conclusions

VCE for CAP has a lower rate of abnormal findings than other indications. However, VCE is a useful diagnostic tool that can help provide a possible etiology of CAP in patients with associated symptoms. However, a change in management from VCE is likely to be limited to those with a history of Crohn’s disease.