Development, characterization and immunogenicity of a multi-stage, multi-valent Plasmodium falciparum vaccine antigen (FALVAC-1A) expressed in Escherichia coli

A synthetic multistage, multi-epitope Plasmodium falciparum malaria antigen (FALVAC-1A) was designed and evaluated in silico, and then the gene was constructed and expressed in Escherichia coli. The FALVAC-1A protein was purified by inclusion body isolation, followed by affinity and ion exchange chromatography. Although FALVAC-1A was a synthetic antigen, it folded to a specific, but as yet incompletely defined, molecular conformation that was stable and comparable from lot to lot. When formulated with four different adjuvants, FALVAC-1A was highly immunogenic in rabbits, inducing not only ELISA reactivity to the cognate antigen and most of its component epitopes, but also in vitro activity against P. falciparum parasites as demonstrated by inhibition of sporozoite invasion, antibody dependent cellular inhibition and the immunofluorescence assay.     

Novel micropelletization technique: highly improved dissolution, wettability and micromeritic behavior of domperidone

The aim of the investigation is to improve the dissolution, wettability, and micromeritic behavior of domperidone, a dopamine antagonist, used in the treatment of nausea and vomiting. Micropelletization technique, a possible approach for ensuring maximum dissolution with enhanced wettability, and uniform pellet size almost spherical so as to achieve the smooth gastric transit of drug have been estimated. Micropellets were prepared utilizing solvent diffusion technique and all the process parameters such as solvent-non-solvent ratio, stirring speed, temperature, and effect of aggregating agent on the micropellets formulation have been optimized. The addition of an aggregating agent (10%v/v of isopropyl alcohol) improved the uniform micropellets formation and the method was reproducible. The micromeritic properties such as size distribution, surface property (using Scalar-USB digital photomicroscope), packability, and flowability of the formulated micropellets were characterized. Fourier transform infrared spectroscopy (FTIR) and Differential scanning calorimetric (DSC) analysis were performed to explain the results. Formulated micropellets showed clear and highly improved in vivo dissolution behavior, probably due to high wettability. The micropelletized drug was stable at room temperature, 25 degrees C/60% relative humidity (RH), and 45 degrees C/70% RH, after 12 weeks.     

Adolescent varicocele: association with somatometric parameters

INTRODUCTION: The developmental changes that occur as a result of puberty have been hypothesized to be important causes of varicocele. Various somatometric parameters were known to affect the occurrence of varicocele during the growth period. We conducted this study in order to examine these relationships and to determine the incidence of varicocele in adolescent males. PATIENTS AND METHODS: We evaluated 1,200 healthy males aged 0-19 years for varicocele and correlated it with the following somatometric parameters: age, height, body mass index (BMI), pubic hair distribution, penile length and testicular volume. RESULTS: Adolescent varicocele was found in 5.6% of the participants. The 13- to 19-year age-group had the highest incidence of varicocele (10.5%). Logistic regression analysis showed that the incidence was positively correlated with age, height and penile length (odds ratio 1.61, 1.04 and 1.37, respectively) and negatively correlated with left testicular volume, BMI and pubic hair distribution (odds ratio 0.87, 0.87 and 0.47, respectively). CONCLUSION: Varicocele was more prevalent in tall boys with a lower BMI, who had quickly progressed through puberty. Our observations suggest that varicocele is associated with various somatometric parameters.     

Metastatic rhinosporidioma in a child

Rhinosporidiosis is a chronic granulomatous disease caused by Rhinosporidium seeberi. It commonly affects nasal mucosa and conjunctiva. Subcutaneous disease is unusual and it is often mistaken for soft-tissue sarcoma. Such tumoral rhinosporidiosis has never been reported in children. This report describes, for the first time, an 11-year-old girl who presented with nasal polyp and multiple metastatic swellings of rhinosporidial origin. Fine-needle aspiration cytology and histopathology were diagnostic. Surgical excision, followed by dapsone therapy, was found to be useful.     

Conformational constraint in oxazolidinone antibacterials. Synthesis and structure-activity studies of (azabicyclo[3.1.0]hexylphenyl)oxazolidinones

The oxazolidinones are a new class of synthetic antibacterials effective against a broad range of pathogenic Gram-positive bacteria, including multi-drug-resistant strains. Linezolid is the first drug from this class to reach the market and has become an important new option for the treatment of serious infections, particularly those caused by methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enteroccocus faecium (VRE). In the search for novel oxazolidinones with improved potency and spectrum, we have prepared and evaluated the antibacterial properties of conformationally constrained analogues in which the morpholine ring of linezolid is replaced with various substituted azabicyclo[3.1.0]hexyl ring systems. Several classes of azabicyclic analogues were identified with activity comparable or superior to that of linezolid. These include analogues bearing hydroxyl, amino, amido, or carboxyl groups on the azabicyclic ring. The azabicyclic acid analogue 50 was 4 times more potent than linezolid against key Gram-positive and fastidious Gram-negative pathogens (S. aureus, Streptococcus pneumoniae, and E. faecalis MICs < or = 1 microg/mL; Haemophilus influenzae MIC = 4 microg/mL).     

Characterization of human IgG repertoires in an acute HIV-1 infection

All known broadly neutralizing antibodies (bnAbs) are highly somatically mutated and therefore significantly differ from their germline predecessors. Thus although the mature bnAbs bind to conserved epitopes of the HIV-1 envelope glycoprotein (Env) with high affinity their germline predecessors do not or weakly bind Envs failing to initiate an effective immune response. The identification of less somatically mutated bnAbs and/or antibody maturation intermediates that are clonally related to bnAbs may be useful to circumvent the major problem of initiating immune responses leading to elicitation of bnAbs. Here, we describe the identification of IgG antibodies from an acutely HIV-1-infected patient using a combination of phage display and high-throughput sequencing. We found two antibodies with only a single point mutation in the V region of their heavy chain variable domains compared to their putative germline predecessors which bound with high affinity to several Envs. They targeted the Env gp41 and did not neutralize HIV-1. Using high-throughput sequencing, we identified several highly abundant CDR3s, germline-like as well as somatically mutated V genes in the VH/VL repertoires of the patient which may provide antibody intermediates corresponding to known bnAbs as templates for design of novel HIV-1 vaccine immunogens.