Intramolecular monomer-on-monomer (MoM) Mitsunobu cyclization for the synthesis of benzofused thiadiazepine-dioxides.

The utilization of a monomer-on-monomer (MoM) intramolecular Mitsunobu cyclization reaction employing norbornenyl-tagged (Nb-tagged) reagents is reported for the synthesis of benzofused thiadiazepine-dioxides. Facile purification was achieved via ring-opening metathesis (ROM) polymerization initiated by one of three metathesis catalyst methods: (i) free metathesis catalyst, (ii) surface-initiated catalyst-armed silica, or (iii) surface-initiated catalyst-armed Co/C magnetic nanoparticles.

A two pulse drug delivery system for amoxicillin: an attempt to counter the scourge of bacterial resistance against antibiotics.

Bearing in mind the present scenario of the increasing biological tolerance of bacteria against antibiotics, a time controlled two pulse dosage form of amoxicillin was developed. The compression coating inlay tablet approach was used to deliver the drug in two pulses to different parts of the GIT after a well defined lag time between the two releases. This was made possible by formulating a core containing one of the two drug fractions (intended to be delivered as the second pulse), which was spray coated with a suspension of ethyl cellulose and a hydrophilic but water insoluble agent as a pore former (microcrystalline cellulose).

Evaluation of novel fusion proteins derived from extracellular matrix binding domains of LigB as vaccine candidates against leptospirosis in a hamster model.

Leptospira binds to host extracellular matrix (ECM) through surface exposed outer membrane proteins called adhesin in order to initiate infection. Of various adhesins present on the surface of the spirochete, Leptospira-immunoglobulin like proteins (Lig proteins) and LipL32 are most abundant, widely distributed among pathogenic serovars and well characterized. Various fragments of Lig proteins (Ligcon4, Ligcon4-7.

Identification of the deleterious 2080insA BRCA1 mutation in a male renal cell carcinoma patient from a family with multiple cancer diagnoses from Pakistan.

Pathogenic germ line mutations in the BRCA1 and BRCA2 genes confer elevated risk of breast and ovarian cancer in females and have a link with variety of cancers other than breast cancer in males. Here we report the first case of a 45-year-old Pakistani male with renal cell carcinoma who was identified to harbor a disease-associated BRCA1 germ line mutation, 2080insA. Detailed description of the family history, clinical presentation and histopathological features of the renal cell carcinoma are presented.

"Click"-capture, ring-opening metathesis polymerization (ROMP), release: facile triazolation utilizing ROMP-derived oligomeric phosphates.

Soluble, high-load ring-opening metathesis polymerization (ROMP)-derived oligomeric triazole phosphates (OTP) are reported for application as efficient triazolating reagents of nucleophilic species. Utilizing a "Click"-capture, ROMP, release protocol, the efficient and purification-free, direct triazolation of N-, O-, and S-nucleophilic species was successfully achieved. A variety of OTP derivatives were rapidly synthesized as free-flowing solids on a multigram scale from commercially available materials.

Immunostimulatory and antigen delivery properties of liposomes made up of total polar lipids from non-pathogenic bacteria leads to efficient induction of both innate and adaptive immune responses.

Novel liposomes prepared from total polar lipids of non-pathogenic bacteria, viz. Leptospira biflexa serovar Potac (designated leptosomes) and Mycobacterium smegmatis (designated smegmosomes) were evaluated for their adjuvant effects with various antigen presenting cells (APCs), viz. murine macrophage cell line, J774A.

Monomer-on-monomer (MoM) Mitsunobu reaction: facile purification utilizing surface-initiated sequestration.

A monomer-on-monomer (MoM) Mitsunobu reaction utilizing norbornenyl-tagged (Nb-tagged) reagents is reported, whereby purification was rapidly achieved by employing ring-opening metathesis polymerization, which was initiated by any of three methods utilizing Grubbs catalyst: (i) free catalyst in solution, (ii) surface-initiated catalyst-armed silica, or (iii) surface-initiated catalyst-armed Co/C magnetic nanoparticles.

Amperometric proton selective sensors utilizing ion transfer reactions across a microhole liquid/gel interface.

A new cost-effective amperometric proton selective sensor utilizing a single microhole interface between two immiscible electrolyte solutions (ITIES) is developed. The sensing methodology is based on measuring currents associated with proton transfer across the interface assisted by a proton selective ionophore. The ellipse shaped micro-interface was first fabricated by simple mechanical punching with a sharp needle on a thin PVC film (12 μm thick) commercially available as a food wrapping material.

Experimental Leptospira interrogans serovar Kennewicki infection of horses.

Background: Little information is available about experimental induction of leptospirosis in horses.

Objectives: Determine serologic, hematologic responses of horses to Leptospira interrogans serovar Kennewicki infection.

Animals: Four adult horses seronegative for leptospirosis.

Cultural interrelationships and the lived experience of Pakistani breast cancer patients.

Aim: There is a paucity of British and international literature on the psychological, sociological and cultural correlates of breast health in ethnic minority women.

Methods: This two centre qualitative study was part of a larger study that aimed to examine the influence of culture on the lived experience of Pakistani Muslim breast cancer patients. Thirty six patients attending hospital out-patient breast cancer clinics in Lahore, Pakistan and London, UK were recruited to the study.

Bioaffinity detection of pathogens on surfaces.

The demand for improved technologies capable of rapidly detecting pathogens with high sensitivity and selectivity in complex environments continues to be a significant challenge that helps drive the development of new analytical techniques. Surface-based detection platforms are particularly attractive as multiple bioaffinity interactions between different targets and corresponding probe molecules can be monitored simultaneously in a single measurement. Furthermore, the possibilities for developing new signal transduction mechanisms alongside novel signal amplification strategies are much more varied.

Identification and characterization of OmpA-like proteins as novel vaccine candidates for Leptospirosis.

Leptospira is an important infectious Gram-negative bacterium causing Leptospirosis in mammals. Outer membrane proteins (OMPs) are key molecules in the interface between the cell and its environment. A group of putative leptospiral outer membrane proteins with an OmpA-like domain, comprising Lp0056, Lp0222, Lp3615, Lp3685, Lp4337 and Lbp328, were identified by bioinformatic methods and expressed as GST-tag fusion proteins.

An 11-year-old girl presenting with chronic knee pain: a case report with diagnostic dilemma.

Discoid meniscus is the commonest anatomical aberration of the knee joint, among rare cases such as bilateral separated lateral meniscus, accessory lateral meniscus, partial deficiency of the lateral meniscus and double-layered lateral meniscus. An 11-year-old girl presented with history of chronic pain in her right knee for the last 6 months. The problem disturbed her involvement in the sport activities at school.

Leptosome-entrapped leptospiral antigens conferred significant higher levels of protection than those entrapped with PC-liposomes in a hamster model.

We prepared novel liposomes from total polar lipids of non-pathogenic Leptospira biflexa serovar Potac (designated leptosomes) and evaluated their vaccine delivery/adjuvant potential with novel protective antigens (Lp0607, Lp1118 and Lp1454) of L. interrogans serovar Pomona in a hamster model. The immune response induced by three individual antigens and protective efficacy were evaluated and compared to those induced by same antigens entrapped with PC-liposomes and E.

Immune response and prophylactic efficacy of smegmosomes in a hamster model of leptospirosis.

Leptospirosis is an important zoonotic disease worldwide. Subunit vaccines are an attractive intervention strategy against this disease, but potent, non-toxic adjuvants are necessary components to any effective vaccine. Among various adjuvant candidates, liposomes have garnered recent attention for their capacity as carriers of vaccines.

The impact of culture and sociological and psychological issues on Muslim patients with breast cancer in Pakistan.

Breast cancer is the most common form of cancer in Muslim women in Pakistan. The impact of the initial diagnosis, culture, religion, and psychosocial and psychological aspects of the disease is not well established. This qualitative study examined the experience and coping strategies used by patients with breast cancer in relation to its impact on their physical, mental health, religious, and family issues.

Immunogenicity and protective efficacy of recombinant Leptospira immunoglobulin-like protein B (rLigB) in a hamster challenge model.

Leptospiral immunoglobulin-like protein (LigB) was truncated into conserved (LigBcon) and variable (varB1, varB2) fragments and expressed as GST/His-tag fusion proteins. Four-week-old hamsters were immunized with equal amounts of each fragment individually or combined in alum adjuvant at days 0 and 21 and subsequently challenged three weeks after the booster with 2.5 LD(50) live virulent Leptospira interrogans serovar Pomona.

Leptospira immunoglobulin-like protein A variable region (LigAvar) incorporated in liposomes and PLGA microspheres produces a robust immune response correlating to protective immunity.

Subunit vaccines are attractive as an intervention strategy against leptospirosis, an important zoonotic disease afflicting both humans and livestock. However, the success of subunit vaccines has been hampered by weak or short-term immunity and unavailability of nontoxic, potent adjuvants. In the present study, the variable region of recombinant Leptospira immunoglobulin like protein A (LigAvar) incorporated into conventional liposomes and PLGA microspheres produced robust immune responses that induced significant protection against virulent Leptospira interrogans serovar Pomona challenge in hamsters.

Evaluation of protective immunity of Leptospira immunoglobulin like protein A (LigA) DNA vaccine against challenge in hamsters.

We demonstrated earlier that immunization with recombinant Leptospira immunoglobulin like protein A (LigA) induced significant protection against virulent Leptospira interrogans serovar Pomona challenge in hamsters. However, the protective immune mechanism remains unclear. In the present study we demonstrated the protective efficacy of a LigA DNA vaccine and evaluated the immune mechanism underlying the protection against leptospirosis in hamsters.

Immunogenicity of the recombinant leptospiral putative outer membrane proteins as vaccine candidates.

Leptospiral putative outer membrane proteins (OMPs) are likely to be essential components of more effective vaccines. Recently completed genomic sequences of Leptospira allowed us to target putative OMPs for the development of recombinant vaccines. We focused on 12 putative OMPs that had no homology with other organisms listed in the NCBI database except MceI and MceII of Leptospira, which are approximately 25% homologous to MceI of Mycobacterium tuberculosis.

Safety, efficacy and pharmacokinetics of tuftsin-loaded nystatin liposomes in murine model.

Present study was performed to evaluate the efficacy, toxicity and pharmacokinetics of antifungal drug nystatin incorporated in immunomodulator tuftsin-bearing liposomes. In vitro toxicity of free nystatin and nystatin incorporated in tuftsin-free or tuftsin-loaded liposomes was assessed by incubation of nystatin formulations with human erythrocytes. The toxicity profile of free nystatin and liposomal formulations of nystatin with or without tuftsin was also analyzed by monitoring the level of blood urea nitrogen (BUN) and serum creatinine in the treated BALB/c mice.

Role of fusogenic non-PC liposomes in elicitation of protective immune response against experimental murine salmonellosis.

Earlier we have demonstrated that novel fusogenic liposomes made up of lipid from Escherichia coli (escheriosomes) have strong tendency to fuse with the plasma membrane of target cells and thereby delivering the entrapped contents into their cytosol. The delivery of entrapped antigen in cytosol of the target cells ensues its processing and presentation along with MHC class I pathway that eventually elicit antigen specific cytotoxic T cells. The result of the present study revealed that immunization of BALB/c mice with escheriosome-encapsulated Salmonella typhimurium (S.

PLGA-microsphere mediated clearance of bilirubin in temporarily hyperbilirubinemic rats: an alternate strategy for the treatment of experimental jaundice.

In the present study, we have demonstrated the suitability of microspheres in removal of plasma bilirubin from systemic circulation of hyperbilirubinemic rats. Poly (lactide co-glycolide) microspheres (PLGA microspheres) have been shown to bind with bilirubin in both a concentration and time dependent manner. The binding affinity of bilirubin to microspheres was enhanced when rat serum albumin (RSA) was loaded into the microspheres.

Binding of bilirubin with albumin-coupled liposomes: implications in the treatment of jaundice.

In the present study, we demonstrated the suitability of liposomes as a method of removing plasma bilirubin in hyperbilirubinemic rats. The liposomes have innate tendency to bind with bilirubin through hydrophobic interaction. Among different types of liposomes, the positively charged liposomes were found to have maximum affinity to free bilirubin.