Immunogenicity study of recombinant human sperm-associated antigen 9 in bonnet macaque (Macaca radiata)

BACKGROUND: The human sperm-associated antigen 9 (hSPAG9) is of special interest attributing to the findings indicating that SPAG9 is an acrosomal molecule. SPAG9 is not only restricted to acrosomal compartment but also persists in equatorial segment post-acrosome reaction, which is a key location in sperm-egg interaction. METHODS AND RESULTS: Immunogenicity studies in macaques were carried out with recombinant hSPAG9 (rhSPAG9) adsorbed on alum, which resulted in high titres of anti-rhSPAG9 antibodies as determined by enzyme-linked immunosorbent assay (ELISA). Immunoblotting analysis employing anti-rhSPAG9 antibodies generated in monkeys indicated that antibodies specifically reacted with native SPAG9 from macaque and human sperm and rhSPAG9 protein. Furthermore, indirect immunofluorescence experiments demonstrated SPAG9 localization in the acrosomal compartment of macaque and human sperm. In addition, monkey antibodies against rhSPAG9 significantly inhibited the human spermatozoa adherence or penetration in zona-free hamster oocytes. CONCLUSION: These results demonstrate that rhSPAG9 adsorbed on alum is highly immunogenic in subhuman primate model and therefore represents a suitable sperm-based vaccine immunogen for fertility trials in macaque.     

Functional polymeric nanoparticles: an efficient and promising tool for active delivery of bioactives

Nanotechnology is a multidisciplinary field and has achieved breakthroughs in bioengineering, molecular biology, diagnostics, and therapeutics. A recent advance in nanotechnology is the development of a functional nanosystem by incorporation, adsorption, or covalent coupling of polymers, carbohydrates, endogenous substances/ligands, peptides, proteins, nucleic acids, and polysaccharides to the surface of nanoparticles. Functionalization confers a wide array of interesting properties such as stealth characteristics, a bioadhesive property, and that it prevents aggregation of nanoparticles, imparts biostability and solubility, reduces toxicity, and provides site-specific delivery. This makes the nanosystem an intelligent tool for diagnostics, prognostics, and controlled and sustained delivery of protein, peptide, pDNA, and other therapeutic agents to specific targets (tissue, cell, and intracellular). Various types of functional nanosystems, such as carbon nanotubes, quantum dots, polymeric micelles, dendrimers, metallic nanoparticles, and liposomes, are being extensively explored. However, high tissue accumulation of nonbiodegradable nanoparticles has caused toxicity problems and rendered them as not-so-popular therapeutic and diagnostic systems. The toxicity and safety of nonbiodegradable nanoparticles are subject to future research. Polymeric nanoparticles have offered attractive alternative modules due to biocompatibility, nonimmunogenicity, nontoxicity, biodegradability, simple preparation methods, high physical stability, possibility of sustained drug release, and higher probability for surface functionalization. Depending on properties that have been modified, polymeric nanoparticles can be grouped in to four classes, namely, stealth, polysaccharide decorated biomimetic, bioadhesive, and ligand-anchored functional polymeric nanoparticles (f-PNPs). This review explores the ligand-anchored f-PNP as a carrier for active delivery of bioactives, envisaged to date. This review also details the ligands available for conjugation, their method of coupling to nanoparticles, and applications of f-PNPs in anticancer drug delivery, oral delivery, gene delivery, vaccine delivery, and intracellular delivery; site-specific delivery to liver, macrophages, lymphatics, and brain; and miscellaneous applications. This review also addresses formidable challenges encountered, and proposes some future strategies for development of a promising site-specific active delivery system.     

Niridazole biodegradable inserts for local long-term treatment of periodontitis: possible new life for an orphan drug

Periodontal pocket inserts of niridazole (NZ) made with Resomer(R) (grades RG 503H and RG858, designated as RH and RG, respectively) were studied. Various formulation variables were evaluated to obtain a biodegradable delivery systems showing device degradation and drug depletion parallel to each other in vitro. Drug release from the prepared inserts was evaluated using a static dissolution setup (for 1 month). Incorporation of 3 parts of RG in 1 part of RH inserts caused a 50% decrease in the initial release rate. The RH-NZ inserts showed a spurt in release around the 10th day of the study, which coincided with the decrease in device weight, suggesting onset of device degradation. Pilot-scale clinical trials in 12 patients indicated improvements in clinical indices from the baseline values. The average pocket depth was reduced significantly (alpha = 0.05) from 6.34 +/- 1.86 mm at baseline to 5.94 +/- 0.28 mm after 28 days of treatment.     

Analgesic, antiinflammatory, and ulcerogenic studies of meloxicam solid dispersion prepared with polyethylene glycol 6000

Meloxicam is a nonsteroidal antiinflammatory drug, used in the treatment of rheumatoid arthritis and oestoarthritis. It is practically insoluble in water, leading to poor dissolution, variations in bioavailability, and gastric irritation on oral administration. In the attempt to reduce its gastric side effect and to increase aqueous solubility, physical mixture and solid dispersion of the drug were prepared with polyethylene glycol 6000. The analgesic, antiinflammatory, and ulcerogenic effects were assessed for physical mixture and solid dispersion in comparison with meloxicam alone. The results indicate that both physical mixture and solid dispersion possess better analgesic and antiinflammatory properties with less ulcerogenic potential when compared with pure meloxicam.     

L-arginine stimulates immune response in chickens immunized with intermediate plus strain of infectious bursal disease vaccine

Infectious bursal disease continues to pose an important threat to the commercial poultry industry, especially after the emergence of virulent infectious bursal disease virus (IBDV). L-arginine, a ubiquitous, basic amino acid is used as an immunostimulant in variety of human and animal studies with great success in immunosuppressed hosts. In the present study, we evaluated the immunomodulatory effects of L-arginine on humoral and cellular immune response in chickens immunized with live intermediate plus (IP) strain of IBDV vaccine. Chickens vaccinated with IP strain and supplemented with 2% L-arginine showed 100% protection after challenge with virulent IBDV compared to 80% protection induced by IP strain alone. IP strain vaccine elicited good antibody titres in both the groups, IP + L-arginine and IP alone, however, the antibody titres in IP + L-arginine group were significantly higher (P < 0.05) than IP vaccinated chickens. Mitogenic response of peripheral blood lymphocytes to specific IBDV antigen stimulation was significantly higher in IP + L-arginine group (P < 0.05). Peripheral blood lymphocytes were able to rapidly clear the suppressive effects of IP strain and virulent challenge virus in IP + L-arginine group. These results strongly suggest that l-arginine plays a vital role in modulation of protective immune response against IBDV.     

L-Arginine stimulates intestinal intraepithelial lymphocyte functions and immune response in chickens orally immunized with live intermediate plus strain of infectious bursal disease vaccine

Infectious bursal disease (IBD) continues to pose potential threat to poultry industry all over the world. The disease can spell disaster not only through its infection but also by break of immunity in chickens vaccinated for other diseases. l-Arginine, a ubiquitous, semi-essential amino acid has emerged as an imunostimulant from variety of human and animal studies. In the present study, we demonstrate the stimulatory effects of l-arginine on intestinal intraepithelial lymphocyte (iIELs) functions as well as on systemic immune response in chickens orally vaccinated with live intermediate plus (IP) strain of IBD vaccine. Challenge studies with virulent IBDV revealed complete (100%) protection in IP+l-arginine group compared with 80% protection recorded in IP strain vaccinated chickens. Functional activities of iIELs evaluated by cytotoxicity assay demonstrated significantly high percentage cytotoxicity in IP+l-arginine groups compared with IP group (P<0.05). Proliferative response of iIELs against IBDV antigen and Con-A was also significantly higher in IP+l-arginine group. Similar results were obtained with peripheral blood mononuclear cell blastogenic response to IBDV and Con-A analyzed as an indicator of systemic cell-mediated immune response. Orally administered IP strain vaccine elicited good antibody titres in both the groups, IP and IP+l-arginine, however, the antibody titres were significantly higher in IP+l-arginine group compared with IP vaccinated group (P<0.05). These results clearly demonstrate that l-arginine stimulates intestinal and systemic immune response against IBDV.     

Comparison of Trace Metals Concentration in PM10 of Different Locations of Lucknow City, India

No abstract available.     

Drug utilization pattern in the intensive care unit of a tertiary care hospital

The authors studied the factors affecting drug use pattern, cost of therapy, and the association between the pattern of drug use and survival as well as the duration of stay in a prospective, observational study in an intensive care unit between February and May 2005. Data were collected regarding drugs used, severity of the disease, and their outcome. The mean +/- SD of the Acute Physiology and Chronic Health Evaluation (APACHE III) and Glasgow Coma Scale (GCS) scores of 84 patients were 52.2 +/- 19.4 and 7.5 +/- 2.4, respectively. Although the mean number of drugs at the time of admission to the intensive care unit was 5.3, it increased to 12.9 on the first day and 22.2 during the entire stay. More than 50% of the average expenditure on drugs and nutrition was accounted by antibiotics. Requirement of insulin or inotropes signified an adverse outcome on mortality (odds ratios of 3.43 and 8.44, respectively). In conclusion, there is a tremendous impact of antibiotic use on the cost of therapy in the intensive care unit. The requirement of certain drugs such as insulin and inotropes is of prognostic significance.     

Preparation, characterization and in vitro dissolution studies of solid dispersion of meloxicam with PEG 6000

The poor solubility and wettability of meloxicam leads to poor dissolution and hence showing variations in bioavailability. The present study is aimed to increase solubility and dissolution of the drug using solid dispersion techniques. The solid binary systems were prepared at various drug concentrations (5-40%) with polyethylene glycol 6000 by different techniques (physical mixing, solvent evaporation). The formulations were characterized by solubility studies, differential scanning calorimetry, fourier transform infrared spectroscopy and in vitro dissolution rate studies. The solubility of drug increased linearly with increase in polymer concentration showing A(L) type solubility diagrams. Infrared spectroscopy studies indicated the possibility of hydrogen bonding with polymer. The differential scanning calorimetry and powder X ray diffraction demonstrated the presence of polymer as eutectica or monotectica in solid dispersion along with the physical characteristics of the drug (crystalline, amorphous or a mixture of both). The solid dispersions of the drug demonstrated higher drug dissolution rates than physical mixtures and pure meloxicam, as a result of increased wettability and dispersibility of drug in a solid dispersion system.     

Adjuvant gemcitabine and concurrent radiation for patients with resected pancreatic cancer: a phase II study

The safety and efficacy of gemcitabine and concurrent radiation to the upper abdomen followed by weekly gemcitabine in patients with resected pancreatic cancer was determined. Patients with resected adenocarcinoma of the pancreas were treated with intravenous gemcitabine administered twice-weekly (40 mg m(-2)) for 5 weeks concurrent with upper abdominal radiation (50.4 Gy in 5(1/2) weeks). At the completion of the chemoradiation, patients without disease progression were given gemcitabine (1000 mg m(-2)) weekly for two cycles. Each cycle consisted of 3 weeks of treatment followed by 1 week without treatment. Forty-seven patients were entered, 46 of whom are included in this analysis. Characteristics: median age 61 years (range 35-79); 24 females (58%); 73% stage T3/T4; and 70% lymph node positive. Grade III/IV gastrointestinal or haematologic toxicities were infrequent. The median survival was 18.3 months, while the median time to disease recurrence was 10.3 months. Twenty-four percent of patients were alive at 3 years. Only six of 34 patients with progression experienced local regional relapse as a component of the first site of failure. These results confirm the feasibility of delivering adjuvant concurrent gemcitabine and radiation to the upper abdomen. This strategy produced good local regional tumour control.